The relationship between potentially traumatic or stressful events, HIV infection and neurocognitive impairment (NCI): a systematic review of observational epidemiological studies.

BACKGROUND: HIV/AIDS and potentially traumatic events (PTEs) or stressful life events (SLEs) and/or PTSD are independently associated with neurocognitive impairment (NCI). Literature suggests that HIV and PTE/SLE exposure independently and consistently affect various domains of cognition including language ability, working memory and psychomotor speed. There are limited data on the interaction between HIV infection and PTEs and their combined effect on NCI. OBJECTIVE: In this systematic review, we synthesise evidence for the combined effect of HIV infection and PTEs and SLEs and/or post-traumatic stress disorder (PTSD) on NCI of people living with HIV/AIDS (PLWHA) from high-, middle- and low- income countries. METHOD: Our inclusion criteria were observational epidemiological studies (case-control, cohort and cross-sectional designs) that investigated the interaction of HIV infection, PTEs and SLEs and/or PTSD and specifically their combined effect on NCI in adults. We searched a number of electronic databases including Pubmed/Medline, PsycINFO, Scopus and Global Health using the search terms: cognition, HIV/AIDS, observational studies, trauma and permutations thereof. RESULTS: Fifteen studies were included in the review, of which the majority were conducted in high-income countries. Ten of the fifteen studies were conducted in the United States of America (USA) and five in South Africa. Seven of these focused on early life stress/childhood trauma. The remaining studies assessed adult-onset PTEs and SLEs only. Eight studies included women only. Overall, the studies suggest that PTE and SLE exposure and/or PTSD are a significant risk factor for NCI in adults living with HIV, with impairments in memory and executive functions being the most likely consequence of PTE and SLE exposure. CONCLUSION: These findings highlight the need for trauma screening and for the integration of trauma-focused interventions in HIV care to improve outcomes.

Antecedentes: El VIH/SIDA y los eventos potencialmente traumáticos (PTEs) o los eventos estresantes de la vida (SLEs) y/o TEPT se asocian independientemente con el deterioro neurocognitivo (NCI). La literatura sugiere que la exposición al VIH, PTE y SLE afecta de manera independiente y consistente varios dominios de la cognición, incluida la capacidad del lenguaje, la memoria de trabajo y la velocidad psicomotora. Hay datos limitados sobre la interacción entre la infección por VIH y los PTE, y su efecto combinado sobre el NCI.Objetivo: En esta revisión sistemática sintetizamos evidencia del efecto combinado de la infección por VIH, PTEs y SLEs, y/o TEPT en el NCI de personas que viven con VIH/SIDA (PLWHA) en países de ingresos altos, medios y bajos.Método: Nuestros criterios de inclusión fueron estudios epidemiológicos observacionales (diseño de caso-control, cohortes y diseños transversales) que investigaron la interacción de la infección por VIH, PTEs y SLEs y/o TEPT, y específicamente su efecto combinado sobre el NCI en adultos. Se realizaron búsquedas en varias bases de datos electrónicas, que incluyeron a Pubmed/Medline, PsycINFO, Scopus y Global Health, utilizando los términos de búsqueda: cognición, VIH/SIDA, estudios de observación, trauma y permutaciones de los mismos.Resultados: Quince estudios se incluyeron en la revisión, de los cuales la mayoría se realizaron en países de altos ingresos. Diez de los quince estudios fueron realizados en los Estados Unidos de América (EE.UU.) y cinco en Sudáfrica. Siete de éstos se centraron en el estrés de la vida temprana/trauma infantil. Los estudios restantes evaluaron PTEs y SLEs cuya aparición fue en la vida adulta solamente. Ocho estudios incluyeron sólo mujeres. En general, los estudios sugieren que la exposición a PTE y SLE y/o TEPT es un factor de riesgo significativo para NCI en adultos que viven con VIH, con el deterioro en la memoria y las funciones ejecutivas como la consecuencia más probable de la exposición a PTE y SLE.Conclusión: Estos hallazgos resaltan la necesidad de la detección de traumas y la integración de intervenciones centradas en el trauma en la atención del VIH para mejorar sus resultados.

[Routine measurement of serum calcitonin in patients with nodular thyroid disorders?]. / Calcitonin-Screening bei der Knotenstruma?

In spite of the fact that the German Society of Endocrinology has recommended calcitonin as screening-parameter the majority of physicians in Germany do not routinely use calcitonin in patients with thyroid nodules to exclude medullary thyroid cancer (MTC). The future revision of the recommendation should describe reference values for each commercially available assay, separately for men and women (basal and after pentagastrin-stimulation), and should define sonomorphological inclusion criteria. The epidemiological database of the prevalence of MTC is controversial and the specificity of basal elevated calcitonin levels is limited up to the 5-fold of the upper reference level. If renal insufficiency, bacterial infection, and an alcohol- or drug-induced stimulation of calcitonin is excluded, hypercalcitoninaemia should be confirmed by a second measurement (if necessary using another assay). Stimulation of calcitonin by use of pentagastrin is mandatory prior to the decision on thyroidectomy. A stimulated calcitonin level < 100 pg/ml justifies "wait and see". If stimulated calcitonin levels range between 100 and 200 pg/ml or higher, the differentiation between C-cell hyperplasia and MTC remains uncertain, especially in men. The implementation of calcitonin-screening requires the definition of sonographic inclusion criteria and validation of each assay. Additional pre-requisites are excellent logistic (short period between blood sampling and start of the laboratory test), knowledge of differential diagnoses, knowledge of the consumption of drugs and alcohol, availability of pentagastrin-testing and of moleculargenetic testing with full information to the patients and sufficient time before the decision on surgery is made. All this and the choice of a skilled surgeon, experienced in thyroidectomy and lymphadenectomy with a low rate of local complications are the rationale to recommend calcitonin-screening primarily in centers for thyroid disorders.

[Confronting the practice of surgery on differentiated thyroid cancer with current guidelines in Germany. A multicenter trial]. / Chirurgische Praxis und Leitlinien beim differenzierten Schilddrüsenkarzinom in Deutschland: ein multizentrischer Vergleich.

AIM: For the surgical therapy of differentiated thyroid cancer precise guidelines are applied by the German medical societies. In a retrospective multicenter study, we investigated the following issues: Are the current guidelines respected? Is there a difference concerning the surgical radicalism and the outcome? Does the perioperative morbidity increase with the higher radicalism of the procedure? PATIENTS, METHODS: Data gained from 102 patients from 17 regional referral hospitals who underwent surgery for thyroid cancer and a following rodioiodine treatment (mean follow up: 42.7 [24-79] months) were analyzed. At least 71 criterias were analyzed in a SPSS file. RESULTS: 46.1% of carcinomas were incidentally detected during goiter surgery. The thyroid cancer (papillary n = 78; follicular n = 24) occurred in 87% unilateral and in 13% bilateral. Papillary carcinomas < 1 cm were detected in 25 cases; in five of these cases (20%) contralateral carcinomas < 1 cm were found. There were significant differences concerning the surgical radicalism: a range from hemithyroidectomy to radical thyroidectomy with lateral neck dissection. Analysis of the histopathologic reports revealed that lymph node dissection was not performed according to guidelines in 55% of all patients. The perioperative morbidity was lower in departments with a high case load. The postoperative dysfunction of the recurrent laryngeal nerve (mean: 7.9% total / 4.9% nerves at risk) variated highly, depending on differences in radicalism and hospitals. Up to now these variations in surgical treatment have shown no differences in their outcome and survival rates, when followed by radioiodine therapy. CONCLUSION: Current surgical regimes did not follow the guidelines in more than 50% of all cases. This low acceptance has to be discussed. The actual discussion about principles of treatment regarding, the so-called papillary microcarcinomas (old term) has to be respected within the current guidelines.

[Guideline for therapy of malignant thyroid tumours: pleading for an actualization]. / Leitlinie zur Therapie maligner Schilddrüsentumoren: Plädoyer für eine Aktualisierung.

Total (or near total) thyroidectomy (TE) followed by radioiodine ((131)I) ablation (RIA) of residual thyroid tissue is considered to be the ideal treatment for differentiated thyroid carcinoma. However, the actual guideline of the DGN (German Society of Nuclear Medicine) recommends for the so-called papillary micro-carcinoma of the thyroid (PMC) no further therapeutic strategy (no complete TE, no (131)I-ablation of the remaining lobe). PMC has been defined as papillary carcinoma measuring 1 cm (T1) in maximal diameter according to the World Health Organization classification system for thyroid tumours (1988). The new WHO-classification (starting in 2003) defines the T1-tumour measuring 2 cm in maximal diameter. The authors demand a new, modern guideline, following the new WHO classification. This includes, that despite the overall excellent prognosis for patients with PMC, the treatment of patients with T1-tumours of the new WHO-classification (including the "old" PMC) should be no different from the treatment of patients with conventional papillary thyroid carcinoma, i.e. complete surgery (TE and central lymph node dissection) followed by RIA of residual thyroid tissue. The authors argue that it is not appropriate to consider the tumour size as the single most important key factor for therapy and prognosis. Even small tumours may have poor prognostic factors, such as lymph node metastasis, multifocality or molecular characteristics (expression of oncogenes).

The influence of differences in hydration on bone-to-soft tissue ratios and image quality in bone scintigraphy.

This prospective study evaluated the effects of different amounts of fluid intake on the bone-to-soft tissue (B:ST) ratio and image quality of bone scans performed using Tc-99m MDP. One hundred sixty patients with no renal disease were divided into three groups with different degrees of hydration in liters (group 1, 0.25 I; group 2, 1 I; group 3, 1.5 I), and image quality was assessed with a semiquantitative score. The B:ST ratio was calculated over the femoral diaphysis and adductor area, respectively. No significant differences in the B:ST ratio or image quality were demonstrated in all three patient groups with median values of 1.90 (group 1), 1.93 (group 2), and 1.84 (group 3). A filled urinary bladder was associated with greater fluid intake. The B:ST and image quality were correlated directly with the postinjection time interval and inversely with age. When patients drink a large volume of fluid, B:ST ratios do not necessarily increase and bone scintigraphy image quality does not improve.

[Combination therapy of endemic goiter with two different thyroxine/iodine combinations]. / Studie zur Kombinationstherapie der endemischen Struma mit zwei unterschiedlichen Thyroxin/Iodkombinationen.

AIM: Of this study was to investigate the extent of thyrotropin (TSH) suppression and volume reduction in combination therapy of endemic goitre. We compared an individually adapted dose of thyroxine with a fixed dose. METHODS: 105 patients of a multicenter study (randomised, single blinded, controlled) received daily a weight-adjusted LT4-dose in combination with 150 micrograms iodide (group A) or a fixed combination of 100 micrograms LT4 plus 100 micrograms iodide (group B), respectively. At the beginning and after 12 weeks TSH-levels and goitre volume were examined. RESULTS: Although the amount of thyrotropin suppression showed no differences in both groups, there were more patients in the weight-adjusted treatment group with completely suppressed thyrotropin serum concentrations (p < 0.05). Both groups showed a reduction of goitre volume of 24% CONCLUSION: A weight-adjusted LT4-dose of 1.4 micrograms/kg body weight often leads to subclinical hyperthyroidism. To obtain low TSH-levels without complete suppression LT4-doses of 1.0 microgram/kg body weight plus 150 micrograms iodide are probably sufficient.

[Value of color-coded Doppler sonography in the differential diagnosis of nodular thyroid gland changes]. / Stellenwert der farbcodierten Doppler-Sonographie in der Differentialdiagnostik nodulärer Schilddrüsenveränderungen.

AIM: The incidence of functional autonomous adenomas, detected in every second nodular goiter by scintigraphic methods is very high in an area of iodine deficiency. The color-coded Doppler sonography (CCDS) as a diagnostic tool in differentiating thyroid nodules is discussed controversially. METHODS: In this prospective study we investigated the value of CCDS in 200 patients with nodular thyroid alterations compared with 99m-Technetium (Tc) scintigraphy. RESULTS: Focal maximas of Tc-uptake were detected in 22.5% of all patients, and 44.5% of the thyroid nodules showed increased vascularity. There was no correlation between nodular vascularity and thyroid 99m-Tc uptake (TcTU). In contrast to this we could demonstrate a significant relation between vascularity and the diameter of the nodule (p < 0.0001). The results are discussed in the context of method specific limitations of ultrasound examinations. CONCLUSION: Our results confirm that CCDS has no great importance in the differentiation of thyroid nodules. Scintigraphy remains the diagnostic method of choice to assess the topographic thyroid function.

Abnormal regional benzodiazepine receptor uptake in the prefrontal cortex in patients with panic disorder.

The neuroanatomical networks involved in the initiation of panic attack and the maintenance of panic disorder are poorly understood. This study aimed to elucidate the possible abnormalities in benzodiazepine receptor uptake in the brain of patients with panic disorder. Seventeen unmedicated patients with panic disorder were investigated using 123I-iomazenil single photon emission tomography (SPET). Seventeen healthy age- and sex-matched volunteers served as controls. The SPET scan was taken 90 min after injection of tracer. Eleven of 17 patients (65%) showed an increased (> 2 S.D. higher than the mean of the controls) right-to-left ratio of benzodiazepine receptor uptake in the prefrontal cortex. Also, the mean right-to-left ratio of benzodiazepine receptor uptake in all 17 patients with panic disorder was higher than in the controls (P < 0.001). Our SPET study demonstrated focally altered benzodiazepine receptor uptake in the prefrontal cortices in patients with panic disorder. Magnetic resonance imaging indicated that the affected region was located in the right middle and inferior frontal gyri. The deterioration in information processing in the right prefrontal cortex may be implicated in the generation of panic disorder.

Tc-99m HMPAO cerebral scintigraphy. A reliable, noninvasive method for determination of brain death.

To determine the usefulness of cerebral blood flow imaging for the diagnosis of brain death, 4 female and 12 male patients, aged 19 to 69 years and suffering from various intracranial lesions, were studied. In addition to neurologic examination, electroencephalographic recording, and cerebral angiography, tomographic brain scintigraphy was performed using a SPECT system with a LEAP collimator after the intravenous administration of 555 MBq Tc-99m HMPAO. The radioisotopic scanning procedure revealed no intracranial perfusion in 14 of the 16 patients. Only minimal cerebellar blood flow was seen in one patient. In another, residual right-sided supratentorial flow was initially present but absent in a follow-up HMPAO SPECT. Carotid angiography (four-vessel contrast media angiography) confirmed the above results without exception. Because HMPAO is taken up by normal brain tissue with no significant redistribution for several hours, the tracer is particularly helpful in cases of suspected brain death. The quality of the tracer must be established by chromatography. Interpretation of the SPECT images produces reliable and reproducible results. In conclusion, cerebral blood flow imaging with HMPAO is a safe, noninvasive procedure for the determination of brain death, that produces fast, reliable, reproducible, and easy-to-interpret results.

Standardized noninvasive assessment of myocardial free fatty acid kinetics by means of 15-(p-iodo-phenyl) pentadecanoic acid (123I-pPPA) scintigraphy: II. Clinical results.

Our results establish that myocardial regions supplied by a significantly stenosed coronary vessel can be distinguished with high statistical significance from healthy regions on account of changes in the myocardium/background ratio, i.e. a reduction of regional uptake of 15-(p-iodo-phenyl) pentadecanoic acid (pPPA). The statistical significance applies to patients with coronary artery disease (CAD), to all examined CAD areas without areas of infarction as well as to infarcted regions. Our results also confirm the suitability of labelled fatty acids, such as pPPA, for the visualization of damaged myocardial regions. The results further indicate that pPPA practically is of comparable value to 201Tl with regard to their respective qualities as 'static' imaging agents for the heart muscle. This study, with the help of a simultaneous analysis of regional myocardial perfusion rates (rMBF) and of a parameter for the metabolism of fatty acids, practised here for the first time, could demonstrate interindividual differences between patients and groups of patients with a correlation between perfusion and the utilization of pPPA in patients with CAD. The reciprocal of the rMBF, the mean transit time (MTT), was significantly prolonged after stress in patients with CAD (P less than 0.05), suggesting impaired 'microcirculation' in the patient group. The determination of elimination half-lives (T1/2) contributes little if any information towards delineation of cardiac disease entities. The wide overlap of T1/2 values between various clinical syndromes and entities with extreme standard deviations remained an annoying problem in our studies. Nevertheless, certain trends in T1/2 behaviour could be recorded, but they did not yield any statistical significances, because of the high degree of individual variability. A considerable variability of T1/2 values among healthy controls was recorded as well as intra-individually in different regions of the heart muscle. The wide range of 'normal' values rendered statistical evaluation almost, if not entirely, impossible. It appears that the high degree of variability results amongst others, from technical shortcomings in the external recording instruments, i.e. gamma cameras, as well as from the presence of interfering alternate substrates such as glucose and lactate. Nevertheless, the wide range of measured results in healthy control subjects suggests the presence of a considerable regional intra-individual heterogeneity of cardiac substrate metabolism. One must therefore accept, at least in our opinion, that T1/2 values are not sufficiently reliable as an indicator of myocardial metabolism and are of little value with respect to clinical diagnostic considerations and to prognosis as well. Possible explanations for this finding are offered and discussed in this paper.

Contribution of thallium-201-SPECT to the grading of tumorous alterations of the brain.

Single photon emission computed tomography (SPECT) with thallium-201-chloride (201Tl) was used in 22 patients to assess the grade of malignancy of brain tumors. Low- and high-grade malignant gliomas could be well differentiated by calculating the Grade Index (GI), i.e., 201Tl uptake in the tumor area relative to a contralateral brain region. Low-grade gliomas (WHO-grade I-II) usually showed a GI of < 1.5. Tumors classified histologically as high-grade malignant (WHO-grade III-IV) had GI values greater than 1.42 and a mean value of 1.89. Until labelled amino-acid tracers for gamma-cameras become commercially available, thallium-201 brain-SPECT can provide an independent and complementary method to CT/MRI for the differential diagnosis of grading of brain tumors. This simple technique can help to reduce sampling errors during needle biopsies of brain tumors, particularly of high-grade lesions incorrectly graded as low-grade tumors due to inadequate biopsy material. In addition, pre- and post-therapy studies can influence the strategy of therapy itself and allow an early detection of recurrences.

[Diagnosis of functional thyroid autonomy]. / Zur Diagnostik der funktionellen thyreoidalen Autonomie.

The diagnosis of thyroidal autonomy is based mainly on quantitative scintigraphy of the thyroid. The specificity of an echopoor pattern in ultrasound for autonomy is low. Also determination of TSH is only half as sensitive as measurement of uptake of 99mTc-pertechnetate under suppression (TcTU-supp) in diagnosing autonomy. For diagnosis and decision about therapeutical consequences of thyroidal autonomy the quantitative scintigraphy under suppression is recommended; side-effects of suppression by Levothyroxin are low.

Semi-quantitative analysis of SPECT with the iodinated fatty acid 15-(ortho-123I-phenyl)-pentadecanoic acid.

15-(ortho-123I-phenyl)-pentadecanoic acid (oPPA) in contrast to the para-isomer pPPA has a prolonged retention in the normal human myocardium. Following qualitative evaluation, a semi-quantitative analysis of oPPA-SPECT is presented in 52 patients (41 with coronary artery disease (CAD) and 11 normals). Data were compared to the results of coronary angiography (CAD patients). Up to 220 MBq 123I-labelled oPPA were injected intravenously after overnight fasting and bicycle exercise. Four minutes later SPECT acquisition (180 degrees technique) was started. In 15 patients a second dose of oPPA was injected 2.5 h later and the study was repeated under rest conditions. Compared to our qualitative analysis the semi-quantitative approach revealed a lower sensitivity of 76% for the detection of CAD (global, stenoses greater than 50%) (specificity was not analysed because the normal patients served as the control group for the calculation of normal values). Because the sensitivity does not exceed that of 201Tl-SPECT or MIBI-SPECT, oPPA is not recommended for the detection of CAD, but it may serve for the evaluation of myocardial viability in ischaemic regions.

[Improvement in nuclear medicine diagnosis of kidney function using 99m technetium mercaptoacetyltriglycine (MAG3)]. / Verbesserung der nuklearmedizinischen Nierenfunktionsdiagnostik durch den Einsatz von 99m-Technetiummercaptoacetyltriglycin (MAG3).

Renal scintigraphy and clearance measurement are indispensable in nephro-urologic disorders. A continuous series of 103 sequential scintigraphies and clearance measurements were performed with the new technetium-labelled agent MAG3 (Gamma-kamera, Phillips Tomo Diagnost) and 131I-orthohippuric acid (OIH) using the Oberhausen method (Nucleopan, Siemens). The time-activity curves obtained with the two radionuclides agreed exactly. Reaching a tubular excretion rate of nearly 90%, the clearance of MAG3 differed by no more than 6% from the OIH clearance in 95% of the cases. The factor between clearances of the two radionuclides was determined by means of a commercially available software according to the Oberhausen method and amounted to 0.59 +/- 0.09. The favorable physical properties and high activity of MAG3 permit exact examination of tubular function and better assessment of renal morphology than hippuran-labelled radionuclides. The low radiation dose combined with a better spatial resolution, especially, the constant availability in a nuclear medicine department should give the preference to MAG3.

Standardized non-invasive assessment of myocardial free fatty acid kinetics by means of 15-(para-iodo-phenyl) pentadecanoic acid (123I-pPPA)scintigraphy: I. Method.

Two simple mathematical functions have been applied for estimating myocardial perfusion and fatty acid metabolism from planar, dynamic 123I-para-phenylpentadecanoic acid (123I-pPPA) studies. The first one uses a modified gamma function and the latter one a biexponential fit. The reciprocal of mean transit time is assumed to represent myocardial blood flow and the fast phase (size and half-time) of the biexponential fit primarily accounts for beta oxidation of 123I-pPPA.

[Are there regional differences in Tc uptake?]. / Gibt es regionale Unterschiede im Tc-Uptake?

The 99mTcO4-uptake (TcTU) was measured in 363 clinically and by laboratory findings euthyroid patients without history of hyper- or hypothyroidism, no evidence of iodine contamination and with a Delta-TSH less than 2.5 IU under a longterm suppressive thyroxine therapy. The medians of TcTU in the different regional groups from the Federal Republic of Germany (mail zip code 2000-8000) were not statistically different from each other, indicating that under suppression with thyroxine the effect of the iodine supply on TcTU is nearly negligible, and that, using the same method, results from different nuclear medicine departments should not differ significantly from each other.

Low dose intraarterial cis-platinum/radiotherapy after local tumour preradiation.

The simultaneous use of intraarterial Cis-Platinum and Radiotherapy (CP/RT) was found to be a very effective and relatively little burdened treatment for a palliative treatment concept. This affects life quality as well as the remission--and survival times. The fast and continual remission with low CP/RT concentrations, even in extreme palliative cases, is surprising. CP/RT treatment shows additive and synergistic effects which are not explainable by the single effects of the cis-platinum dose used (60 mg/1.73 m2 in our case) or the total irradiation dose (e.g., 5 Gy TD) or the fractionation (e.g., 5 X 1 Gy), especially since the doses of each which were used are by themselves without therapeutic relevance. Only the combination of the modalities with a low dose two-day preradiation program induced the described effects.

Tomographic studies of rCBF with 99mTc-HM-PAO SPECT in comparison with PET in patients with primary brain tumors.

99mTc-hexamethyl-propyleneamine-oxime (HM-PAO) was developed as a radiotracer of regional cerebral blood flow (rCBF) with SPECT. THe purpose of this study was to investigate if HM-PAO is able to trace rCBF in primary brain tumors. In 10 patients with glioblastoma grade IV the intracerebral distribution of HM-PAO was studied in comparison with C15O2 steady state inhalation technique and PET for rCBF evaluation. In all instances the cerebral HM-PAO distribution was comparable with rCBF pattern as confirmed by a significant correlation of tumor to cortex ratios. The results indicate the clinical usefulness of HM-PAO for tracing rCBF in brain tumors.