Age changes in the centrally and peripherally located sensory neurons in rat

Summary Lipofuscin pigment formation and distribution in the Mes. N.5 neurons, trigeminal and spinal ganglia of male Wistar rats of 2, 14, 32 and 49 months as an indication of aging has been investigated. These intraneuronal pigment granules are found as early as 2 months in all the cells, and continue to accumulate in all the cells in varying amounts until the first year of life. The different rate at which lipofuscin accumulates probably shows the difference in the maturation of the functionally related cells. At later stages the obvious findings are complex pigment body formation and localization of the pigment bodies either at one pole as seen in the Mes. N. 5 neurons or arranged submembranously parallel to the long axis of the cells in the ganglia. The vacuolated lipofuscin pigment bodies are bound by a double limiting membrane and among the vacuoles are found tubular membranous structures resembling residual mitochondrial substructures. These findings suggest a mitochondrial origin of lipofuscin, rather than a lysosomal. The intracellular pigment bodies seen in the perineuronal satellite cells of peripheral ganglia appear to be signs of removal of lipofuscin from the ganglion cells. Acknowledgements. We wish to thank Mr. J. Kirchhoff, Miss E. Heyder, Mr. W. Dresp and Mrs. M. del C. Weinrichter for the technical assistance, Mr. R. Dungan and Mrs. S. Ruelke for the photographic work. We are grateful to the DAAD and the Universitätsbund of the University of Göttingen for the financial assistance. This work was supported by the Deutsche Forschungsgemeinschaft, Grant No. G1 28, 16/17.DAAD fellow on leave from the Department of Anatomy, A.I.I.M.S., New Delhi 16, India.     

A method for stereotactic laser microsurgery in the treatment of deep-seated CNS neoplasms

Intracranial tumors are reconstructed in stereotactic space by means of computerized axial tomographic data. The intracranial tumor is operated on with the patient in the stereotactic frame using a carbon dioxide laser to approach the lesion and vaporize it. Ultimately, a gas-filled cavity results which can be monitored on AP and lateral radiographs. Vaporization continues until the cavity produced is superimposable on the coronal and sagittal CT reconstruction. 2 cases treated by this method are presented.     

Computer-assisted stereotactic biopsy of intracranial lesions

The use of a computer program that allows the integration of stereotactically gathered CT, MRI and digital angiographic data in the planning of a biopsy trajectory is described. This system has been used to perform 447 stereotactic biopsies in 439 patients. Intracranial hemorrhages occurred in three patients; combined morbidity and mortality was less than 1%. Incorporation of angiographic data and visualization of the surgical trajectory enhances the safety and accuracy of stereotactic biopsy of intracranial lesions.     

Cytology of neuroectodermal tumors of the brain in crush preparations. A review of 56 cases of deep-seated tumors sampled by CT-guided stereotactic needle biopsy

Fifty-six brain tumors of neuroectodermal origin were sampled by computed tomographic stereotactic needle biopsy. Crush preparations prepared from tiny tissue fragments displayed distinctive cytologic characteristics of different tumor types in 77% of the cases. The adjunctival value of crush preparations to frozen section diagnosis is discussed, and the cytologic features of different types of neuroectodermal brain tumors in crush preparations are illustrated.     

Diagnosis and treatment of brainstem mass lesions by CT-guided stereotactic surgery

Current neuroradiographic techniques including computed tomographic scanning (CT) and magnetic resonance imaging (MRI) when added to the clinical neurologic examination can localize precisely even small lesions within the brainstem. While the clinical-radiographic diagnosis is accurate with respect to locale, it is often in error with respect to the pathologic nature of the solitary brainstem lesion. Therefore, empiric treatment without the benefit of a tissue diagnosis will often be inappropriate. CT-guided stereotactic surgery can safely and reliably provide a tissue diagnosis in such cases. Furthermore, in selected cases, therapeutic interventions can be of substantial and lasting benefit to the patient.     

Computed tomography-guided fine needle aspiration biopsy of deep-seated lesions. A four-year experience

With the increased sophistication of radiologic imaging techniques, the sensitivity of detecting nonpalpable, deep-seated lesions has greatly improved. Coupling these techniques with fine needle aspiration biopsy (FNAB) provides a cost-effective, minimum-risk, highly sensitive and specific method of diagnostically evaluating the lesions. Over a four-year period (1985-1989) a total of 2,229 FNABs were performed at Loyola University Medical Center, Chicago; 539 of these biopsies were computed tomographically guided. The geographic computed tomographic biopsy sites were: thorax, 267 (49.54%); abdomen, 175 (32.47%); and retroperitoneum, 97 (18%). Four hundred eighty FNAB cases were diagnostic, with subsequent histologic follow-up in 284 (58%) cases. Fifty-nine (10.9%) FNABs were unsatisfactory; of them, 31 had subsequent diagnostic histology, and 9 remained unsatisfactory. A good correlation between FNAB and histology was observed, with an overall sensitivity of 93.2%, specificity of 98.8%, false-negative rate of 6.8% and false-positive rate of 1.2%. Diagnostic pitfalls and biopsy adequacy in computed tomographically guided FNABs are discussed.     

Different occurrence rates of centrally located cytoplasmic granulation in one cohort oocytes show distinctive embryo competence and clinical outcomes

Centrally located cytoplasmic granulation (central granulation) is a common cytoplasmic dysmorphism in human oocytes retrieved after controlled ovarian hyperstimulation (COH). In order to achieve a better understanding of its formation and effects on clinical outcomes, we retrospectively analyzed 422 ICSI treatment cycles. Three groups of patients were classified according to the ratio of central granulation occurrence in one egg cohort, as partial granulation, all granulation and control groups. The partial granulation group had a significantly lower BMI and higher AMH level compared to the control or all granulation groups. Consistent with these distinctive features in the partial granulation group, fertilization and blastocyst formation rates were reduced significantly in the partial granulation group but not in the all granulation group. Furthermore, the clinical outcomes in fresh embryo transfer cycles were dramatically reduced in the partial granulation group compared with the control group. However, in FET cycles, all three clinical outcomes were significantly reduced in the all granulation group but not in the partial granulation group. We propose that partial granulation may reflect a specific population of patients, and that the central granulation structure is sensitive to cryopreservation.     

Prospective study of combined use of bronchial aspirates and biopsy specimens in diagnosis and typing of centrally located lung tumours.

OBJECTIVE--To determine the diagnostic accuracy of examining bronchial secretions in pulmonary cytopathology and whether cytology and histopathology can complement each other in routine practice among lung specialists. DESIGN--A prospective study comparing 1225 cytological and biopsy results, conducted during 1987-93. Tumours were confirmed by histopathology, imaging techniques, or clinical outcome and imaging techniques combined. SETTING--11 lung or internal medicine units, France. SUBJECTS--1128 patients (874 men; 254 women) aged 65.3 (SD 13.7) years who underwent fibreoptic bronchoscopy for various pulmonary symptoms. RESULTS--Exact concordance between cytological and biopsy results was obtained in 1036/1187 (87.3%) satisfactory specimens. In all 574 lung tumours were diagnosed. One case (0.08%) was a false positive cytological diagnosis in a patient with tuberculosis. Patients with lung cancer were more likely to have positive cytological results than positive biopsy results (P < 0.001). Agreement in tumour typing was observed in 375/424 (88.4%) cases, when non-small cell carcinomas, small cell carcinomas and undifferentiated carcinomas were separated. In the 11 patients with squamous cell carcinomas in situ, eight (72.7%) of the carcinomas were diagnosed cytologically as squamous cell. Unsatisfactory material was obtained in only 20 (1.6%) and 19 (1.6%) cases by cytology and biopsy respectively. Examinations had to be repeated in 86 (7.6%) patients. CONCLUSIONS--Examination of bronchial secretions complements histopathology in both diagnosing and typing lung tumours and could be performed more systematically in patients undergoing fibreoptic bronchoscopy.     

Dosimetric analysis of Tomotherapy-based intracranial stereotactic radiosurgery of brain metastasis

PurposeThis paper analyzes Tomotherapy-based intracranial stereotactic radiosurgery (HTSRS) of brain metastasis targeting two end-points: 1) evaluation of dose homogeneity, conformity and gradient scores for single and multiple lesions and 2) assay of dosimetric criticality of completion of HTSRS procedures.Methods42 treatment plans of 33 patients (53 brain lesions) treated with HTSRS were analyzed. Dose to healthy brain, homogeneity, conformity and gradient indexes were evaluated for each lesion. Influence of Field Length and multiple lesions cross-talk effect were assessed. Treatment interruption and completion was investigated using radiochromic films in order to examine the delivered dose and its robustness to patient intrafraction movement.ResultsThe average dose homogeneity index was 1.04 ± 0.02 (SD). Average dose conformity and gradient score indexes were 1.4 ± 0.2 and 50 ± 14 respectively. We found a strong correlation of the dose to healthy brain and conformity and gradient indexes with target(s) volume for which analytical functions were obtained. Field Length and cross-talk effect were significantly correlated with poor gradient scores, but were found not to affect dose conformity.ConclusionsHomogeneity and conformity of HTSRS plans achieved excellent scores, while dose falloff and dose to healthy brain were slightly larger when compared with non-coplanar SRS techniques. Care should be given if treating large (>3 cc) or multiple near in-plane lesions in order to reduce dose to healthy brain. Analysis of interrupted treatments suggests splitting HTSRS treatments in two consecutive fractions in order to prevent target miss and overdosage due to patient intrafraction movement.     

CT-guided stereotactic biopsies of lesions in the medulla and a case of Leigh's disease

CT-guided stereotactic biopsy of lower brain stem lesions in 7 consecutive cases is discussed. A frontal transincisural approach was used. Five patients had astrocytomas histologically. The single patient who had undergone empirical radiation therapy prior to tissue diagnosis revealed only necrosis. One patient was found to have pathology suggestive of Leigh's disease. This patient was not radiated and is the first alive adult to have this diagnosis confirmed. Although controversy still exists in the management of brain stem lesions, we intend to demonstrate the value of tissue diagnosis in the management of such lesions.     

The effects of centrally administered neuropeptides on the development of gastric lesions in the rat

Centrally administered neuropeptides were investigated for their effects on the development of gastric lesions in rats. Thyrotropin releasing hormone (TRH), vasoactive intestinal peptide (VIP) and gonadotropin releasing hormone (LHRH) produced gastric lesions acutely, with TRH demonstrating the most pronounced effect in terms of incidence and severity. Ten-fold higher doses of the same peptides administered intravenously produced none or very few gastric lesions. Moreover, pretreatment with atropine partially inhibited their production. Corticotropin releasing factor (CRF) exhibited only mild ulcerogenic effects, and the gastric lesions induced with this peptide developed more slowly than with TRH, VIP and LHRH. Although ulcerogenic in their own right, none of these four neuropeptides significantly potentiated the potent ulcerogenic effects of cold-restraint stress. Since other neuropeptides, including somatostatin, human pancreatic growth hormone releasing factor (hpGRF), substance P, bombesin, and neurotensin, had no demonstrable effects on gastric mucosa, we can conclude that the lesions were not a general effect of intracisternal administration of neuropeptides. The results suggest that within the central nervous system, there are several neuropeptides that play a significant role in the development of gastric lesions via, at least in part, vagal-dependent mechanisms.     

Choice of radioisotope in stereotactic interstitial radiotherapy of small brain tumors

In stereotactic interstitial radiotherapy, small radioactive sources are placed within the brain tumor to deliver locally high radiation doses. The choice of the radioisotope depends upon the dose distribution around the isotope, energy of the emitted radiation, relative biological effectiveness, and finally, the cost and availability of the isotope. We have analyzed 198gold, 125iodine and 192iridium in terms of these four factors. Our results have shown that 125I is superior to the other two isotopes due to its soft X-rays and dosimetric as well as radiobiological properties. Unfortunately, it is the most expensive of these radioisotopes, and can be difficult to obtain in specific activities.     

Stereotactic biopsy for deep-seated intracerebral lesions. Correlation between computer tomography, positron emission tomography and electrophysiological activity

In 16 cases of stereotactic deep brain biopsy, a correlative study was made by computer tomography, positron emission tomography, and electrophysiological depth recording. This multimodal study is shown to be of great value in stereotactic biopsy of deep-seated cerebral lesions.     

Aldosterone acts centrally to increase brain renin-angiotensin system activity and oxidative stress in normal rats

Aldosterone acts upon mineralocorticoid receptors in the brain to increase blood pressure and sympathetic nerve activity, but the mechanisms are still poorly understood. We hypothesized that aldosterone increases sympathetic nerve activity by upregulating the renin-angiotensin system (RAS) and oxidative stress in the brain, as it does in peripheral tissues. In Sprague-Dawley rats, aldosterone (Aldo) or vehicle (Veh) was infused for 1 wk via an intracerebroventricular (ICV) cannula, while RU-28318 (selective mineralocorticoid receptor antagonist), Tempol (superoxide dismutase mimetic), losartan [angiotensin II type 1 receptor (AT(1)R) antagonist], or Veh was infused simultaneously via a second ICV cannula. After 1 wk of ICV Aldo, plasma norepinephrine was increased and mean arterial pressure was slightly elevated, but heart rate was unchanged. These effects were ameliorated by ICV infusion of RU-28318, Tempol or losartan. Aldo increased expression of AT(1)R and angiotensin-converting enzyme (ACE) mRNA in hypothalamic tissue. RU-28318 minimized and Tempol prevented the increase in AT(1)R mRNA; RU-28318 prevented the increase in ACE mRNA. Losartan had no effect on AT(1)R or ACE mRNA. Immunohistochemistry revealed Aldo-induced increases in dihydroethidium staining (indicating oxidative stress) and Fra-like activity (indicating neuronal excitation) in neurons of the hypothalamic paraventricular nucleus (PVN). RU-28318 prevented the increases in superoxide and Fra-like activity in PVN; Tempol and losartan minimized these effects. Acute ICV infusions of sarthran (AT(1)R antagonist) or Tempol produced greater sympathoinhibition in Aldo-treated than in Veh-treated rats. Thus aldosterone upregulates key elements of brain RAS and induces oxidative stress in the hypothalamus. Aldosterone may increase sympathetic nerve activity by these mechanisms.     

Pulmonary segmental resection for solitary lesions of doubtful character

Pulmonary cancer can be diagnosed earlier if patients with pulmonary symptoms of chronic type are given x-ray examination early, if patients over 40 years of age have a yearly roentgen examination of the chest regardless of their state of health, and if those with acute pulmonary illness are examined by x-ray within one month of the onset of illness. Observation of a known intrapulmonary lesion of unknown character should never last for more than one month. If it persists after that period, complete investigation, including thoracotomy, should be carried out if necessary to establish an exact diagnosis. A localized intrapulmonary lesion can be removed by segmental resection so that all healthy functioning lung is conserved if the disease is benign. If, after pathological examination, the lesion is shown to be cancerous, more radical resection can be carried out.     

Treatment of low malignancy brain neoplasms by means of stereotactic interstitial radiotherapy

The authors report their results of 37 patients with low malignancy brain tumors seated in deep or highly functional areas not amenable to traditional surgery, nor to conventional radiochemotherapy. In the past 5 years these patients were treated by means of stereotactic interstitial radiotherapy. The isotope employed in all cases was 125I. Stereotactic radioisotope implants were always preceded by multiple stereotactic biopsies affording precise histological diagnoses. A 6-month to 5-year follow-up shows a survival rate of 72.6% (29 patients), and of these patients, 80.9% (26 out of 29) had complete social reentry.     

Remission spectrometry for blood vessel detection during stereotactic biopsy of brain tumors

Stereotactic biopsy is used to enable diagnostic confirmation of brain tumors and treatment planning. Despite being a well‐established technique, it is related to significant morbidity and mortality rates mostly caused by hemorrhages due to blood vessel ruptures. This paper presents a method of vessel detection during stereotactic biopsy that can be easily implemented by integrating two side‐view fibers into a conventional side‐cutting biopsy needle. Tissue within the needle window is illuminated through the first fiber; the second fiber detects the remitted light. By taking the ratio of the intensities at two wavelengths with strongly differing hemoglobin absorption, blood vessels can be recognized immediately before biopsy sampling. Via ray tracing simulations and phantom experiments, the dependency of the remission ratio R = I₅₇₈/I₆₅₀ on various parameters (blood oxygenation, fiber‐to‐vessel and inter‐fiber distance, vessel diameter and orientation) was investigated for a bare‐fiber probe. Up to 800–1200 µm away from the probe, a vessel can be recognized by a considerable reduction of the remission ratio from the background level. The technique was also successfully tested with a real biopsy needle probe on both optical phantoms and ex‐vivo porcine brain tissue, thus showing potential to improve the safety of stereotactic biopsy.

Dual‐wavelength remission measurement for the detection of blood vessels during stereotactic biopsy.