Corticosterone does not cause testicular toxicopathology in the rat: relevance to methylxanthines, ACTH and stress.

1. Methylxanthines, ACTH and stress are well known to produce testicular pathology (e.g. seminiferous tubule atrophy). Methylxanthines, ACTH and stress alter hormone secretion, particularly from the pituitary-adrenocortical system. Consequently, it has recently been suggested that there may be a causal relationship between changes in endogenous physiological adrenocortical secretions, particularly corticosterone, and testicular pathology. 2. This study tested the hypothesis that corticosterone mediates the testicular effects of both methylxanthine treatment and stress. Corticosterone was administered daily by subcutaneous injection to groups of 10 male rats at dose levels of 2 or 20 mg kg-1 in propylene glycol (1 ml kg-1) for 1 month (the shortest duration of methylxanthine or ACTH exposure known to produce testicular pathology). The highest dose of corticosterone resulted in plasma concentrations that closely matched values resulting from stress (200-700 ng ml-1) compared with controls (< 25 ng ml-1). 3. The highest dose of corticosterone caused reduced body weight gain, lower thymus, adrenal, seminal vesicle and prostate weights, but did not induce any testicular pathology. 4. That a high, but physiologically relevant, dose of corticosterone did not cause testicular pathology in this experiment excludes this steroid in the direct aetiology of methylxanthine, ACTH and stress-induced testicular pathology. Other steroids secreted from the adrenal, in combination with corticosterone, may be involved.     

Rapid isolation of human CD34 hematopoietic stem cells--purging of human tumor cells.

Human CD34+ hematopoietic stem cells were purified using a new technology in which monoclonal antibodies are covalently immobilized on polystyrene surfaces. The CD34+ cell isolation scheme involved three sequential processes: (1) purification of bone marrow mononuclear cells; (2) enrichment of CD34+ cells using covalently immobilized soybean agglutinin; and (3) positive selection of CD34+ cells using polystyrene surfaces coated with the anti-CD34 monoclonal antibody ICH3. CD34+ cells purified by this process have both low-to-medium forward light scatter and low 90 degrees light-scatter properties. Moreover, the purified CD34+ cells are greater than 85% viable, express appropriate characteristic surface antigens, and are 10-50-fold enriched in short- and long-term hematopoietic activity. CD34+ cells collected in this manner from bone marrow samples contaminated with radiolabeled breast carcinoma, neuroblastoma, acute myelogenous leukemia, or small cell lung carcinoma cells were 99.9% depleted of the tumor cells. The CD34+ cell selection devices are sterile and are easily scaled-up to process clinical scale bone marrow samples.     

Digital echocardiography in myocardial infarction

Probably the most under-utilised application of echocardiography is in patients with coronary artery disease (CAD). This under-utilisation is striking since echocardiography can be very valuable in evaluating the natural history and therapy of CAD. One reason why echocardiography is not being utilised to its fullest is because of the reliance on videotape to record and display echocardiograms. This medium is time consuming and inconvenient for clinicians to review studies, it is not ideal for detecting subtle wall motion abnormalities, and videotape is impractical for comparing serial studies. Recording and storing echocardiograms on a digital medium overcomes these difficulties. Digital cine loops of single cardiac cycles provide great versatility. Multiple views or studies can be displayed simultaneously, subtle changes in wall motion are more easily detected and different views, or serial studies, can be readily compared. Such images can be displayed on computers on the ward or in the coronary care unit (CCU) and be available 24 hours a day, seven days a week at the convenience of the clinician. One does not need to find a recording on a two hour videotape, which may be in the ultrasound instrument, and one can view the exam in 30 sec instead of 5 to 10 min. Regional and global left ventricular function is one of the most important manifestations of CAD. With new therapeutic efforts at restoring myocardial function and limiting infant expansion, assessing LV function is more important than ever. Digital echocardiography is an extremely practical and convenient way for clinicians to obtain this information.     

Watershed infarcts in the fetal and neonatal brainstem. An aetiology of central hypoventilation, dysphagia, M?ibius syndrome and micrognathia.

Watershed zone infarcts of the human cerebral cortex at the overlapping junctions of the anterior and middle cerebral arterial territories are well known. Another watershed zone exists in the brainstem tegmentum, between the terminal perfusion zones of the paramedian penetrating and long circumferential arteries, which are paired segmental vessels arising from the basilar artery. The vertebrobasilar circulation achieves its mature configuration and caudorostral flow by 9 weeks gestation. Systemic hypotension and other conditions of reduced basilar perfusion in the fetus, either early or late in gestation, may result in symmetrical longitudinal columns of infarction in the midbrain and tegmentum of the pons and medulla oblongata and laminar necrosis of the midbrain tectum. Within this zone are cranial nerve nuclei III-XII, the nucleus and tractus solitarius or central pneumotaxic center, as well as the nucleus ambiguus and other somatic motor nuclei that subserve muscles of swallowing, mastication and tongue movement. Watershed infarcts in the human fetal and neonatal brainstem are clinically expressed as multiple cranial neuropathies, failure of central respiratory drive and apnea, dysphagia and aspiration, M?bius syndrome and Pierre Robin sequence. MRI is sometimes helpful, but most of the involved neuroanatomical structures are beneath the resolution of present imaging techniques, and the diagnosis during life depends upon clinical neurological examination of the neonate, sometimes supported by evoked potential studies. Postmortem examination confirms the diagnosis and dates the lesions, but also contributes to better understand transient or persistent vascular insufficiencies in the fetal and neonatal brainstem.     

Postoperative Cognitive Dysfunction in Patients with Preoperative Cognitive Impairment: Which Domains Are Most Vulnerable?

Background: The authors explored the database of the first International Study of Postoperative Cognitive Dysfunction study to specify the domains of cognitive function that were most vulnerable and to determine the pattern of deterioration in patients with preoperative cognitive impairment.

Methods: One thousand two hundred eighteen patients were included in the first International Study of Postoperative Cognitive Dysfunction, where neuropsychological testing was performed at entry to the study, at 1 week, and at 3 months after surgery. The authors' analyses determined the extent to which seven neuropsychological measures changed after surgery with focus on the relation with preoperative cognitive impairment, defined as a preoperative score 1.5 SD below healthy controls in the memory test.

Results: Preoperative cognitive impairment was found in 74 patients at baseline. At 1 week, cognitive deterioration was seen in all tests, but in particular in the Letter Digit Coding and the time of the Stroop interference test, with 14% and 16% of the total sample (n = 1,016) exceeding 2 SD, respectively. At 3 months, deterioration was more uniform. Significantly fewer in the preoperative cognitive impairment group had deterioration in the memory test, both at 1 week and at 3 months, with no patient displaying a deterioration exceeding 2 SD.     

Salivary gland malignancy with divergent differentiation: is it a teratocarcinosarcoma?

Four poorly differentiated malignant lesions occurred in a 60-year-old Chinese male in the nasal cavity, submandibular gland, a lymph node in the neck, and the mandible. These malignant lesions developed within an 8-year period and each showed distinctive histological features. Among these malignant lesions, the neoplasm in the submandibular gland presented variegated histological and immunohistochemical (IHC) features and posed a diagnostic challenge in interpretation. Based on microscopic and IHC findings, we believe the diagnosis of teratocarcinosarcoma is justified for the submandibular neoplasm and the metastasis in the lymph node. The pathological features and diagnoses of these malignant lesions are discussed.