Tuberculous mastoiditis - a case series.

SUMMARY: Tuberculous mastoiditis (TBM) is a rare form of extrapulmonary tuberculosis (TB), which may result in catastrophic complications, including mastoid and ossicle destruction, hearing loss and intracranial spread if untreated. Diagnosis is challenging due to the paucibacillary nature of extrapulmonary TB, compounded by limited theatre access for specimen retrieval, resulting in delayed diagnosis and treatment initiation. In this case series, we discuss three cases of TBM (one paediatric and two adults) who presented to the public and private healthcare sectors in the Eastern Cape in 2022, underscoring that TB does not respect socioeconomic status.

Chia Seeds Oil Suppresses the Resistance of Hepatocellular Carcinoma Cells to Liposomal-doxorubicin and Upregulates the Tumor Suppressor miRNAs.

BACKGROUND: Chia seed is an oil seed with multiple biological activities. Doxorubicin is effective chemotherapy for liver cancer. Resistance and adverse effects are doxorubicin limitations. OBJECTIVE: This study aimed to investigate the effect of chia seeds oil (CSO) on the resistance of HepG2 cells to liposomal-doxorubicin (DOX). METHODS: The objective were investigated through measuring cytotoxicity, doxorubicin-metabolizing enzyme Cytochrome P450 3A4 (CYP-3A4), multidrug resistance-associated protein (MRP1), and the expression of multiple tumor suppressor microRNAs. RESULTS: The findings indicated that low concentration of CSO increased HepG2 cells' sensitivity to DOX, as concluded from its higher cytotoxicity. DOX-induced mRNAs of CYP-3A4 and MRP1 and their protein levels. CSO inhibited both in DOX-treated cells. CSO-induced tumor suppressor miRNAs. Doxorubicin inhibited miR-122 and let-7/b/e expression, while it led to overexpression of let- 7a. CSO/DOX upregulated let-7/b/e, miR-34a, and miR-122 (which inhibits MRP1) and downregulated let-7a, which may lead to increased apoptosis. CONCLUSION: CSO effectively re-sensitized HepG2 cells to liposomal-doxorubicin via inhibiting MRP1 and CYP-3A4, which may increase in vivo doxorubicin bioavailability and decrease its therapeutic dose to diminish its adverse effects.

Exploring physiologic reactions to persuasive information.

Persuasion aims at changing peoples' motivations and/or behaviors. This study explores how and when physiology reflects persuasion processes and specifically whether individual differences in motivations and behaviors affect psychophysiologic reactions to persuasive information. Participants (N = 70) with medium or high meat consumption patterns watched a persuasive video advocating limited meat consumption, while their electrodermal and cardiovascular physiology was measured. Results indicated that the video increased participants' moral beliefs, perceived behavioral control, and reduction intentions. This study also found an increase in physiologic arousal during the persuasive video and that people with motivations less aligned to the persuasion objective had more physiologic arousal. The findings encourage further psychophysiologic persuasion research, especially as these insights can potentially be used to personalize persuasive messages of behavior change applications.

[Irreversible loss of brain function : Requirements and Clinical diagnosis]. / Irreversibler Hirnfunktionsausfall : Voraussetzungen und Klinische Diagnostik.

Brain death (irreversible loss of brain function), according to German regulations, is investigated exclusively by qualified specialists in a strictly hierarchical three-step pattern and a four-eyes principle. In step 1 all necessary prerequisites are to be checked and the pathophysiology of brain damage has to be classified. Step 2 comprises the clinical investigation of reactivity to external stimuli and the upper, middle and lower brain stem reflexes including apnea testing. Step 3 exclusively checks for irreversibility of this condition. The latter is achieved by appropriate technical investigations or by repeated clinical examinations within context-specified intervals (range 12-72 h). However, exclusion of contributing primarily infratentorial pathologies is necessary to avoid limitations of the clinical findings. In this paper, both the initiation of brain death diagnostics and the approved clinical tests regarding to their execution, their alternatives and limits are presented and special situations like conditions with extracorporeal membrane oxygenation (ECMO) are also examined.

Spermidine: A predictor for neurological outcome and infarct size in focal cerebral ischemia?

BACKGROUND AND PURPOSE: Polyamines are mainly restricted to the intracellular space. During focal cerebral ischemia, polyamines are released from the intracellular compartment. Experimental studies have implicated a marked elevation in brain tissue and blood. The aim of our study was to investigate whether the elevation of polyamines in the blood of patients with focal cerebral ischemia correlates with the clinical outcome and the infarct volume. METHODS: Polyamines were measured in 16 patients with focal cerebral ischemia and in 8 healthy control subjects. Blood samples for polyamine measurement were taken at admission and at fixed time points for the next 28 days. Polyamines were analyzed in red blood cells by a high-pressure liquid chromatography system. Clinical findings were recorded with the NIH Stroke Scale score. Volume of infarction was analyzed from cranial CT at admission and on days 4 to 6 after ischemia. RESULTS: A significant increase of the spermidine level in the peripheral blood could be observed in all patients with focal cerebral ischemia as compared with control subjects (P:<0.01), starting with the admission. Spermidine values correlated positively with the clinical outcome at several time points in the first 48 hours (r=0.90 to 0.40; P:<0.01) and with the infarct volume in cranial CT on days 4 to 6 (r=0.91; P:<0.01). CONCLUSIONS: As hypothesized from experimental data, polyamine levels in blood increase in patients after focal cerebral ischemia. The results indicate that the peripheral spermidine level is closely associated with the clinical outcome as well as with the infarction volume. Therefore, polyamines may be used as a novel predictor for the prognosis of patients with focal cerebral ischemia.

Hyperglycemia delays terminal depolarization and enhances repolarization after peri-infarct spreading depression as measured by serial diffusion MR mapping.

We investigated the effect of hyperglycemia on the initiation and propagation of spreading depression-like peri-infarct ischemic depolarization (SD) induced by focal cerebral ischemia in rats. Peri-infarct SD were monitored during the initial 15 minutes after remotely induced middle cerebral artery occlusion (MCAO) using serial diffusion weighted magnetic resonance imaging. Maps of the apparent diffusion coefficient (ADC) were calculated and ADC decreases were monitored over time. Hyperglycemic rats (n = 6) had a significant prolongation of the time from induction of MCAO to the start of the ADC decrease as compared with normoglycemic control rats. The time to the maximal ADC decrease was significantly delayed and recovery of transient ADC declines in the area adjacent to the ischemic core was significantly faster in hyperglycemic rats. We conclude that hyperglycemia delays the terminal depolarization in the ischemic core and supports a faster repolarization in severely mal-perfused penumbral tissue after SD, which reflects the increased availability of energy substrates in the state of hyperglycemia.

Regional distribution of ornithine decarboxylase activity and polyamine levels in experimental cat brain tumors.

Biosynthesis of the polyamines putrescine, spermidine, and spermine, and activation of the first key enzyme ornithine decarboxylase (ODC) are closely associated with cellular proliferation. In the present study, the distribution of ODC activity and polyamine levels was investigated for the first time regionally in experimental brain tumors of the cat. Brain tumors were produced by stereotactic xenotransplantation of rat glioma cells. Twenty days after implantation, the brains were frozen in situ, cut into slices, and cryostat sections and tissue samples were taken to determine ODC activity and polyamine levels biochemically. The quantified data were color-coded to present the regional distribution of ODC activity and polyamine levels in the respective section. ODC activity significantly increased in some areas within the tumor, whereas peritumoral tissue showed no difference to the non-tumoral, contralateral hemisphere. This increase turned out in parallel to a high number of mitoses in the same tumor parts (r=0.861). Putrescine levels increased both, in the whole tumor and in the peritumoral edema. Regional differences in putrescine content did not correlate with solid and proliferative parts of the tumor. Spermidine and spermine levels were only slightly increased in some parts of the tumor. Thus, these experiments show the close correlation of a high mitotic rate and activation of ODC within experimental gliomas and underline the relevance of ODC as a biochemical marker of proliferation in brain tumors.

Surveillance of nosocomial infections in a neurology intensive care unit.

To identify overall and site-specific nosocomial infection (NI) rates in patients receiving neurological intensive care therapy, a prospective study was started in 1997 in the ten-bed neurological intensive-care unit (NICU) of the University Hospital of Freiburg, Germany. Case records and microbiology reports were reviewed twice a week, and ward staff were consulted. NI were defined according to the Center for Disease Control and Prevention (CDC) criteria and were categorised by specific infection site. Within 30 months, 505 patients with a total of 4,873 patient days were studied (mean length of stay: 9.6 days). 122 NI were identified in 96 patients (74 patients with one, 18 with two and 4 with three infections. An incidence of 24.2/100 patients and incidence density of 25.0/1,000 patient days of NI in the neurological ICU were documented. Site-specific incidence rates and incidence densities were: 1.4 bloodstream infections per 100 patients (1.9 central line-associated BSIs per 1,000 central line-days), 11.7 pneumonias per 100 patients (20.4 ventilator-associated pneumonias per 1,000 ventilator-days), 8.7 urinary tract infections per 100 patients (10.0 urinary catheter-associated urinary track infections (UTIs) per 1,000 urinary catheter-days). Additionally, 0.4 cases of meningitis, 0.8 ventriculitis, and 1.2 other infections (catheter-related local infection, diarrhea) were documented per 1,000 patient days. 15% of nosocomial pathogens were A. baumannii (due to a outbreak of an nosocomial pneumonia with A. baumannii), 13% S. aureus, 10% E. coli, 7% CNS,7% Bacteroides spp., 7% Enterobacter spp., 6,5% Klebsiella spp.,5.9% enterococci, 5.9% streptococci, and 4.7% Pseudomonas spp. In eight cases of NI no pathogen could be isolated. In future, data on NI in NICUs should be assessed in greater detail, both to improve the quality of care and serve as a basis for identification and implementation of the most effective measures by which to prevent these infections in patients receiving intensive neurological care.

Comparison of flow disturbances in small carotid atheroma using a multi-gate pulsed Doppler system and Doppler color flow imaging.

The capacity of a multi-gate pulsed Doppler (MPD) system and Doppler color flow imaging (DCFI) for the evaluation of flow patterns was studied in 14 patients with 17 nonstenotic carotid plaques (luminal narrowing less than 40%). Plaque morphology was assessed by means of a high-resolution B-mode system with subsequent three-dimensional reconstruction of the lesion surface. MPD velocity profiles obtained proximally, centrally and distally to the plaque (51 analyses) were normal in 31 sites corresponding to 28 undisturbed and 3 turbulent flow patterns assessed by Doppler color flow imaging (90% specificity). Of the 10 irregular MPD flow profiles, DCFI detected turbulence in 7 (70% sensitivity). 10 asymmetric MPD waveforms without irregularities were normal in 7 and turbulent in 3 DCFI studies. These results suggest, that MPD is superior to DCFI for the detection of nonturbulent flow asymmetry nearby small carotid plaques. However, DCFI displays turbulence with a high specificity and reasonable sensitivity and visualizes the morphologic-hemodynamic interaction in carotid atherosclerosis simultaneously.

Comparison of transcranial Doppler flow velocity and cerebral blood flow during focal ischemia in rabbits.

The predictive value of transcranial Doppler (TCD) cerebral blood flow velocity (CBFV) measurements for cerebral blood flow (CBF) calculations in humans is still controversial, and experimental correlative studies are lacking. The aim of the present study was to validate TCD signals of CBFV during focal cerebral ischemia. Therefore, CBFV determined in the middle cerebral artery (MCA) was compared with values of CBF obtained from autoradiograms of ischemic brain areas. To determine CBFV, a transcranial Doppler ultrasound probe (TCD) adapted to small sample volumes was used in 9 rabbits. CBF was quantified after a final infusion of [14C]-iodoantipyrine in the same animals. For focal cerebral ischemia induction, two threads were flushed upward simultaneously into the internal carotid artery, resulting in a flow reduction in the ipsilateral MCA. After thread occlusion, mean systolic CBFV in the MCA decreased from 49 +/- 9 cm/s to 22 +/- 3 cm/s. CBF in the caudate nucleus was reduced (19 +/- 8 mL/100 g/min) compared to the contralateral nonischemic side (52 +/- 18 mL/100 g/min). The decrease in hemispheric CBF correlated well with the decrease in both mean systolic (r = 0.97) and diastolic (r = 0.94) CBFV in the MCA (p < 0.01). The decrease in CBFV determined by transcranial Doppler ultrasound in the MCA appears to reflect the reduction in CBF in the affected brain hemisphere and can be used as a quantitative in vivo parameter for tissue perfusion.

[Palliative sedation in a man with oral cancer; the Royal Dutch Medical Association guidelines not always sufficient]. / Palliatieve sedatie bij een man met mondkanker: KNMG-richtlijn is niet altijd toereikend.

BACKGROUND: Palliative sedation is an effective treatment option in patients with refractory symptoms in the last phase of life. In 2009 the Royal Dutch Medical Association (KNMG) published revised guidelines. The dosage of propofol recommended in these guidelines is, however, based on one single study. CASE DESCRIPTION: A 60-year-old patient with a history of psychiatric disease and alcohol abuse was admitted to the palliative care unit suffering from unbearable pain from a squamous carcinoma of the floor of the oral cavity. Adequate treatment of his symptoms was initially possible, but when his symptoms became refractory we initiated continual sedation. Adequate symptom control was only achieved when propofol was administered in a high dosage of 150 mg/h and levomepromazine administration was reinitiated. CONCLUSION: In our opinion the advised starting dose of propofol is too low, especially in comparison with sedation in regional anaesthesia described in the literature. Furthermore, we advocate that administration of drugs from step 2, midazolam and levomepromazine, is not discontinued when propofol sedation is commenced in step 3.

Prevalence, molecular characterization, and phenotypic confirmation of extended-spectrum beta-lactamases in Escherichia coli, Klebsiella pneumoniae, and Klebsiella oxytoca at the Radboud University Nijmegen Medical Centre in The Netherlands.

The prevalence and molecular types of extended-spectrum beta-lactamases (ESBLs) were determined during a 1-year period in unselected clinical nonduplicate isolates of Escherichia coli (n = 1,738), Klebsiella pneumoniae (n = 436), and Klebsiella oxytoca (n = 208), cultured at the University Medical Centre Nijmegen, The Netherlands. Isolates identified as ESBL producer by the Phoenix automated system were collected prospectively and subjected to molecular analysis for the most common ESBLs TEM, SHV, and CTX-M, as well as OXA and GES. Both the Etest ESBL and double-disk synergy test were performed as confirmatory tests. The estimated prevalence of ESBLs was 2.1% in E. coli, 5.2% in K. pneumoniae, and 2.4% in K. oxytoca. TEM-12 and -26, SHV-5 and -12, and CTX-M groups 1 and 9 were the most frequent ESBLs found. Isolates identified as ESBLs by the Phoenix were confirmed by polymerase chain reaction (PCR) in only 42%. In ESBL PCR-positive E. coli and K. pneumoniae, both confirmatory tests were positive in 95% of the isolates. In 28% of the Etest and 13% of the double-disk synergy test-positive isolates, PCR could not detect any ESBL gene. In these cases, other resistance mechanisms may play a role. Confirmatory tests were unreliable for K. oxytoca. A previously described mutation in the K1 enzyme was detected in one ceftazidime-resistant K. oxytoca. The prevalence of ESBLs in The Netherlands is increasing. The predominant molecular types of ESBLs detected were comparable to other studies. Phoenix ESBL results need to be confirmed as advocated by ESBL detection guidelines.

Fulminant acute disseminated encephalomyelitis mimicking acute bacterial menigoencephalitis.

Most patients with acute disseminated encephalomyelitis (ADEM) recover quickly under corticosteroid treatment and have a favourable long-term prognosis. We report on a young woman with acute onset of an extensive and solitary white-matter lesion in the left hemisphere. Fever, high pleocytosis and elevated protein in cerebrospinal fluid initially suggested bacterial meningoencephalitis. The patient died from brain herniation despite maximal conservative therapy. Histological changes in necropsy were consistent with the diagnosis ADEM. Treatment options of fulminant ADEM are discussed.

Compensatory carotid artery dilatation in early atherosclerosis.

BACKGROUND: From pathological studies of coronary arteries, it has been recognized that progressive plaque development may be compensated for by an increase of the arterial diameter. However, the dynamics of this process have not been investigated, and it is not known whether compensatory dilatation is a general pathomechanism in human arteries. METHODS AND RESULTS: Using a high-resolution duplex scanner and subsequent three-dimensional plaque reconstruction, we prospectively studied the effect of carotid plaque development on the vascular geometry in 32 patients at 6- to 12-month intervals. Plaque progression in 41% (n = 26) of studies was associated with an increase of the vessel diameter between 0.4 and 1.2 mm in 76% (n = 20). Among 36 unchanged plaque developments, enlargement of the arterial diameter was assessed in only 28% (n = 10) (P < .001). CONCLUSIONS: Our data suggest that increasing plaque volume is significantly associated with enlargement of carotid artery segments, which compensates for arterial narrowing in early stages of the disease.

High resolution quantitative relaxation and diffusion MRI of three different experimental brain tumors in rat.

The potential of quantitative parameter images of the relaxation times T1 and T2, the proton density rho and the apparent diffusion coefficient (ADC) to characterize three different experimental rat brain tumors (F98 glioma, RN6 Schwannoma, and E376 neuroblastoma) was studied. All parameter values, as determined in histologically confirmed regions of interest (ROI), were higher in edema than in tumor, which in turn were elevated with respect to normal brain. ROI values of ADC and T2 delivered statistically significant (P < 0.01) differentiation between tumor and edema. Multidimensional parameter combinations improved differentiation between different tissues. However, the three tumor types could not be differentiated. All parameter maps allowed the identification of the whole tumor-edema area. On T2 images, edema could be identified best, whereas the tumor itself was hardly visualized. In many cases, tumor presentation using T1 maps corresponded best with histology, nevertheless suffering from a poor tumor-edema differentiation.

Localization of experimental brain tumors in MRI by gadolinium porphyrin.

The contrast between edema and F98 glioma in rat brain was distinctly enhanced in T2-weighted MRI (TE 130 ms, TR 3 s) by intraperitoneal injection of the synthetic gadolinium-porphyrin complex, GdTPPS. The T1 relaxation time of the gliomas was selectively shortened by about 50% from 1339 +/- 109 ms to 628 +/- 106 ms, and the T2 relaxation time was shortened by about 35% from 86 +/- 6 ms to 57 +/- 5 ms. The relaxation times of normal tissues under investigation (cortex, corpus callosum, temporal muscle, ventricles) were unaltered. Therefore, GdTPPS-application causes F98 gliomas to appear hyperintense in T1-weighted MRI and hypointense in T2-weighted MRI.

Selective enhancement of experimental rat brain tumors with Gd-TPPS.

The synthetic metalloporphyrin gadolinium (III)-tetraphenylporphine sulfonate (TPPS) was successfully used as a contrast agent for in vivo magnetic resonance (MR) imaging of rat brain glioma. After injection of Gd-TPPS, the signal intensity of experimental rat brain glioma distinctly increased on T1-weighted MR images, an effect similar to that produced by the clinically applied MR imaging contrast agent gadolinium diethylenetriaminepentaacetic acid (DTPA). In contrast to other contrast agents studied (Gd-DTPA, manganese [III]-TPPS), Gd-TPPS produced hypointensity in glioma on T2-weighted images. The tumor-selective accumulation of paramagnetic Gd-TPPS in glioma shortened T1 by 53%, from 1,315 msec +/- 199 to 628 msec +/- 106, and T2 by 34%, from 86 msec +/- 4 to 57 msec +/- 5 (2 days after injection of 0.25 mmol/kg Gd-TPPS). The relaxation times of normal cortex, striatum, corpus callosum, and temporal muscle were not significantly affected. As a result, gliomas appeared hyperintense on T1-weighted images and hypointense on T2-weighted images. Owing to the strong effect of Gd-TPPS on the T2 of glioma, normal brain tissue, tumor, and peritumorous edema could be distinguished on T2-weighted images alone.

Acute hepatic encephalopathy with diffuse cortical lesions.

Acute hepatic encephalopathy is a poorly defined syndrome of heterogeneous aetiology. We report a 49-year-old woman with alcoholic cirrhosis and hereditary haemorrhagic telangiectasia who developed acute hepatic coma induced by severe gastrointestinal bleeding. Laboratory analysis revealed excessively elevated blood ammonia. MRI showed lesions compatible with chronic hepatic encephalopathy and widespread cortical signal change sparing the perirolandic and occipital cortex. The cortical lesions resembled those of hypoxic brain damage and were interpreted as acute toxic cortical laminar necrosis.

Diffusion-weighted MR imaging of experimental brain tumors in rats.

Diffusion-weighted magnetic resonance imaging was used for the description of experimental brain tumors in rat. To validate this approach, diffusion-weighted images (DWI) were compared with native T1- and T2-weighted images, and with T1-weighted images following contrast enhancement with the tumor-specific contrast agent manganese (III) tetraphenylporphine sulfonate (MnTPPS). Three tumor types were studied: F98 glioma, RN6 Schwannoma, and E376 neuroblastoma. On heavily diffusion-weighted images, all three tumor types as well as the peritumoral edema were clearly hypointense with respect to the intact brain tissue. T2-weighted images presented mainly peritumoral edema as hyperintense region. A clear demarcation of the tumor was possible only on T1-weighted images after contrast enhancement with MnTPPS. The difference in signal intensity between tumor and homotopic regions in the contralateral hemisphere was comparable in DWIs and in contrast-enhanced T1-weighted images. Spatial comparison of depicted lesion areas in all three imaging modalities indicated that hypointense region on DWI represents both tumor and edema but does not permit their spatial differentiation.

Quantitative diffusion MR imaging of cerebral tumor and edema.

The detection of brain tumors using standard techniques of qualitative, relaxation-weighted magnetic resonance imaging (MRI) requires the application of contrast agents. We investigated whether or not it is possible to use diffusion-weighted MRI to localize tumors without contrast enhancement. Three different experimental rat brain tumors were studied: F98 glioma, RN6 Schwannoma and E376 neuroblastoma. We found a marked hypointensity in the region of the tumor and edema in heavily diffusion-weighted images, which corresponded well with the histological presentation. Quantitative maps of the apparent diffusion coefficient (ADC) allowed a better localization of the tumor than that obtained by regional presentation of T2 times, particularly under conditions in which peritumoral edema was absent. The ADC differences of the three tumor types were statistically not significant. Based upon regions-of-interest evaluations, tumor could be distinguished from peritumoral edema and normal brain tissue. However, a sharp demarcation between tumor and peritumoral edema was not possible, and this is attributed to a similar enlargement of interstitial space. It was concluded that diffusion-weighted MRI possesses a high potential for the detection of brain tumors but does not allow precise demarcation of the tumor border.