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.

[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.

Impaired dynamic cerebral autoregulation in eclampsia.

Eclampsia is frequently associated with brain edema, cerebral infarction or hemorrhage. Its underlying cerebrovascular pathophysiology is still poorly understood. We examined cerebral autoregulation by a non-invasive multimodal assessment in a 28-year-old primaparous woman with postpartal eclampsia. Transcranial Doppler sonography showed considerably increased cerebral blood flow velocity (CBFV) of all basal cerebral vessels. Magnetic resonance imaging demonstrated multifocal vasogenic brain edema. Using transfer function analysis, a severely decreased phase shift between respiratory-induced 0.1-Hz oscillations of arterial blood pressure and CBFV was observed, indicating substantial disturbance of dynamic cerebral autoregulation (DCA). In contrast, CO(2)-vasomotor reactivity of the right middle cerebral artery was only slightly reduced. We therefore assume that the cerebral arteriolar dysfunction in eclampsia leads primarily to an impairment of the autoregulatory mechanism that is followed by different degrees of arteriolar vasodilation. Because of its probably high sensitivity to hemodynamic disturbances, assessment of DCA might be of great value in early pre-eclampsia for risk prediction of cerebral arteriopathy and eclampsia.

Chlamydia pneumoniae DNA in peripheral venous blood samples from patients with carotid artery stenosis.

In the study presented here, peripheral blood specimens obtained from patients with atherosclerosis were examined for the presence of Chlamydia pneumoniae to determine whether these specimens can be used for routine testing. Chlamydia pneumoniae DNA was detected in 7 of 56 patients with carotid stenosis and in three of four patients with other atherosclerotic diseases, but it was not detected in any of 50 healthy controls or in any of 59 age- and gender-matched patients suffering from other nonatherosclerotic diseases. IgG antibodies indicative of an active Chlamydia pneumoniae infection were detected by microimmunofluorescence in two of nine PCR-positive patients but in none of 41 PCR-negative patients. Four of nine serum samples obtained from PCR-positive patients contained IgA antibodies compared to 5 of 41 samples obtained from PCR-negative patients.

Hyperglycemia in patients with focal cerebral ischemia after intravenous thrombolysis: influence on clinical outcome and infarct size.

The aim of the present prospective study was to investigate whether hyperglycemia influences the clinical outcome or the infarct size after intravenous thrombolysis of focal cerebral ischemia. A consecutive series of hyperglycemic (n = 14) and normoglycemic patients (n = 17) with acute focal cerebral ischemia (<3 h) in the middle cerebral artery (MCA) territory received rtPA (0.9 mg/kg body weight) intravenously. Clinical outcome was measured using the NIH Stroke Score on admission and was followed up until day 28. Infarct volume was measured by diffusion-weighted MR imaging on admission, on days 3 and 7. There was a significantly better neurological outcome on day 28 in the normoglycemic patients than in the hyperglycemic group (NIH SS 4.0 versus 7.4; p < 0.05). The infarction volume increased significantly in the hyperglycemic patients Delta = 39.9 plus minus 17.4% compared to normoglycemic patients Delta = 27.1 plus minus 14.1% (p < 0.05). The present study suggests that hyperglycemia in patients with a focal MCA ischemia can cause a worse clinical outcome despite recanalization of the occluded vessel by thrombolysis therapy. This correlates with a markedly larger increase of the infarction volume in the hyperglycemic group. These results may be explained by an accentuated lactate accumulation and pH decrease by elevated energy levels which cannot be compensated by restoration of blood flow 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.

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.

Polyamine metabolism in brain tumours: diagnostic relevance of quantitative biochemistry.

OBJECTIVE: Activation of polyamine metabolism is closely associated with cellular proliferation. The purpose was to investigate whether the content of the polyamines putrescine, spermidine, and spermine, and the activity of the first metabolic key enzyme of polyamine metabolism, ornithine decarboxylase (ODC), represent biochemical markers of malignancy in brain tumours. METHODS: The concentration of putrescine, spermidine, and spermine, and the activity of ODC were biochemically quantified in tissue samples obtained during open microsurgery of 670 patients with brain tumours. Biochemical analysis and histopathological classification were carried out in serial tumour samples. RESULTS: The activity of ODC was very low in peritumoral non-neoplastic brain tissue (0.9 (SD 0.6) nmol/g/h). It was significantly higher in gliomas and it significantly increased with a higher grade of malignancy (grade I 2.7 (2.8) nmol/g/h, grade II 3.1 (4.0) nmol/g/h, grade III 5.7 (5.6) nmol/g/h, grade IV 10.6 (11.7) nmol/g/h). High enzyme activity was also found in medulloblastomas (25.5 (15.1) nmol/g/h), malignant lymphomas (52.1 (42.1) nmol/g/h), and metastases from carcinoma (14.9 (22.1) nmol/g/h). Lowest values were measured in epidermoid cysts (0.5 (0.2) nmol/g/h), craniopharyngiomas (1.2 (0.9) nmol/g/h), angioblastomas (1.6 (1.7) nmol/g/h), and neurinomas (2.0 (1.8) nmol/g/h). By contrast with ODC activity, polyamine concentrations did not correlate with the grade of malignancy. Correlation of regional biochemical and histomorphological data in rapidly growing neoplasms showed high enzyme activity in solid tumour parts and low activity in necrotic areas. CONCLUSIONS: Novel data relating ODC activation and polyamine concentrations to neuropathology is presented indicating that high ODC activity represents a biochemical marker of malignancy in brain tumours. This information is important for clinical and therapeutic investigations.

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.

Tuberculous meningoencephalitis in HIV-seronegative patients: variety of clinical presentation and impact on diagnostics and treatment.

UNLABELLED: Tuberculous meningoencephalitis (TBM), an infrequent disease in Western European countries, shows a wide heterogeneity of clinical symptoms. MATERIAL AND METHODS: We present 4 patients (age range 42-72 years) with the definite diagnosis of isolated TBM. All patients were HIV-seronegative, only 1 patient was known to be immunoincompetent on admission due to acute myelocytic leukemia; other reasons for immune suppression were detected in 2 other patients (leukemia and idiopathic CD4+ T-lymphocytopenia, respectively). RESULTS: The diagnosis of TBM was confirmed in 3 cases by culture from CSF, in 1 case Mycobacterium tuberculosis was proven only in tracheal aspirate. In 1 patient M. bovis was found, which is an extremely rare cause of TBM in Germany. We report the contributions of different diagnostic tools (CSF analysis, neuroimaging) in reaching the presumptive diagnosis and in monitoring the further course. All patients developed neurological complications despite prompt tuberculostatic treatment. Three of the patients presented a chronic severe loss of consciousness of unclear origin. CONCLUSION: The possible causative relationships of these complications and their impact on the prognosis are discussed.

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 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.

Impairment in preattentive visual processing in patients with Parkinson's disease.

We explored the possibility of whether preattentive visual processing is impaired in Parkinson's disease. With this aim, visual discrimination thresholds for orientation texture stimuli were determined in two separate measurement sessions in 16 patients with idiopathic Parkinson's disease. The results were compared with those of 16 control subjects age-matched and 16 young healthy volunteers. Discrimination thresholds were measured in a four-alternative spatial forced-choice paradigm, in which subjects judged the location of a target embedded in a background of distractors. Four different stimulus configurations were employed: (i) a group of vertical targets among horizontal distractors ('vertical line targets'); (ii) targets with varying levels of orientation difference on a background of spatially filtered vertically oriented noise ('Gaussian filtered noise'); (iii) one 'L' among 43 '+' signs ('texton'), all of which assess preattentive visual processing; and (iv) control condition, of one 'L' among 43 'T' distractors ('non-texton' search target), which reflects attentive visual processing. In two of the preattentive tasks (filtered noise and texton), patients with Parkinson's disease required significantly greater orientation differences and longer stimulus durations, respectively. In contrast, their performance in the vertical line target and non-texton search target was comparable to that of the matched control subjects. These differences were more pronounced in the first compared with the second session. Duration of illness and age within the patient group correlated significantly with test performance. In all conditions tested, the young control subjects performed significantly better than the more elderly control group, further indicating an effect of age on this form of visual processing. The results suggest that, in addition to the well documented impairment in retinal processing, idiopathic Parkinson's disease is associated with a deficit in preattentive cortical visual processing.

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.