"Juvenile stress" alters maturation-related changes in expression of the neural cell adhesion molecule L1 in the limbic system: relevance for stress-related psychopathologies.

L1 is critically involved in neural development and maturation, activity-dependent synaptic plasticity, and learning processes. Among adult rats, chronic stress protocols that affect L1 functioning also induce impaired cognitive and neural functioning and heightened anxiety reminiscent of stress-induced mood and anxiety disorders. Epidemiological studies indicate that childhood trauma is related predominantly to higher rates of both mood and anxiety disorders in adulthood and is associated with altered limbic system functioning. Exposing rats to stress during the juvenile period ("juvenile stress") has comparable effects and was suggested as a model of induced predisposition for these disorders. This study examined the effects of juvenile stress on rats aversive learning and on L1 expression soon after exposure and in adulthood, both following additional exposure to acute stress and in its absence. Adult juvenile-stressed rats exhibited enhanced cued fear conditioning, reduced novel-setting exploration, and impaired avoidance learning. Furthermore, juvenile stress increased L1 expression in the BLA, CA1, DG, and EC both soon after the stressful experience and during adulthood. It appears that juvenile stress affects the normative maturational decrease in L1 expression. The results support previous indications that juvenile stress alters the maturation of the limbic system and further support a role for L1 regulation in the mechanisms that underlie the predisposition to exhibit mood and/or anxiety disorders in adulthood. Furthermore, the findings support the "network hypothesis," which postulates that information-processing problems within relevant neural networks might underlie stress-induced mood and anxiety disorders.

Improved verbal learning after outpatient oral physostigmine therapy in patients with dementia of the Alzheimer type.

BACKGROUND: Previous investigators have reported improvements in verbal learning in outpatients suffering from dementia of the Alzheimer type (DAT) when they were treated daily with oral physostigmine for periods of days to months. Questions remain, however, regarding both the specificity of the induced cognitive changes and the time course of the biological activity of the drug when physostigmine was used to treat DAT patients. We examined both of these parameters in an outpatient, double-blind, placebo-controlled study that examined the effect of physostigmine on memory and other cognitive functions. METHOD: Eight DAT patients were treated for 3 weeks with oral physostigmine administered four times daily in a double-blind, crossover, placebo-controlled study. An auditory verbal learning test (AVLT) was administered to assess verbal learning. Digit span, word fluency, and frequency of intrusions served as controls for nonspecific changes in attention and verbal responsiveness. RESULTS: AVLT scores improved after drug administration compared with scores for baseline and placebo performances (p = .04). Other measures were unchanged. Improvement was unrelated to the time interval between memory testing and last ingested dose. CONCLUSIONS: These results indicate a longer period of biological activity for physostigmine than previously considered and extend previous reports of improved verbal learning after oral physostigmine treatment to a more convenient dosing schedule. These results suggest further that the improvements induced by physostigmine result specifically from enhancement of long-term memory processes.

The occurrence of different intrusive errors in patients with Alzheimer's disease, multiple cerebral infarctions, and major depression.

Recent evidence suggests that specific types of intrusive errors may occur more often in the protocols of Alzheimer's disease (AD) patients than in those of patients diagnosed with other types of dementia. Using the FULD Object Memory Evaluation, we documented the occurrence of five qualitatively different types of intrusive errors for mildly and moderately impaired patients with AD and multiple cerebral infarctions (MCI). Depressed and normal elderly controls were also studied. Despite an equivalent degree of impairment on a broad array of neuropsychological measures, mildly impaired AD patients evidenced greater deficits on a measure tapping retrieval from semantic memory and demonstrated a higher occurrence of specific types of intrusive errors relative to their mildly impaired MCI counterparts. Further, both of these measures were highly correlated, suggesting that these indices may be particularly sensitive to semantic dysfunction associated with early AD.

Leukocyte alkaline phosphatase and carcinoembryonic antigen in metastatic colorectal cancer patients.

Peripheral blood leukocyte alkaline phosphatase scores and plasma carcinoembryonic antigen levels in 26 patients with metastatic colorectal cancer were compared to those in 30 healthy controls. Patients had metastases to the liver and abdomen. The mean leukocyte alkaline phosphatase score in the metastatic colorectal cancer patients was significantly higher than in the control group (246 +/- 65 vs, 52 +/- 26, p less than 0.001); and the mean carcinoembryonic antigen level in the patients was also significantly higher than in the controls (110 +/- 100 vs, 4.9 +/- 3 ng/ml, p less than 0.001). One hundred percent of the metastatic cancer patients had elevated LAP scores and 73% of these patients had elevated CEA levels. There was a difference between the mean CEA levels in the patients with liver metastases and those with abdominal metastases (162 +/- 135 vs, 39 +/- 53 ng/ml, p less than 0.04). The results suggest that although both markers were elevated in metastatic colorectal cancer, the LAP score seems to be more useful in detecting metastatic disease, since we found 11% false negatives with the CEA level and 0% false negatives with the LAP score.

Leukocyte alkaline phosphatase score in patients with cerebrovascular disease and in patients with primary and metastatic brain tumors.

Leukocyte alkaline phosphatase (LAP) activity in peripheral blood was determined in 54 patients with cerebrovascular disease (CVD), 11 patients with primary brain tumor, and 23 patients with metastatic brain tumor. The LAP score of the primary brain tumor patients (155 +/- 40) was significantly higher (P less than 0.03) than the LAP score for cerebrovascular disease patients (96 +/- 87). The LAP score levels of the metastatic brain tumor patients (251 +/- 55) was significantly higher as compared with both the cerebrovascular disease (P less than 0.001) and primary brain tumor groups (P less than 0.001). The LAP score could serve as an additional, although non-specific, marker to assist in the differentiation between cerebrovascular disease and brain tumors.

Leukocyte alkaline phosphatase and carcinoembryonic antigen in colorectal cancer patients (usefulness in the assessment of the stage).

Leukocyte alkaline phosphatase (LAP) scores in peripheral blood, and plasma carcinoembryonic antigen (CEA) levels were determined in 122 colorectal cancer patients, and compared to 30 healthy persons, who served as controls. Both markers are gradually elevated according to the severity of tumor penetration. LAP scores in Dukes'C and D (157 +/- 79) were significantly higher than in Dukes'A, B1 and B2 (81 +/- 43), p less than 0.001. CEA levels were also higher in Dukes'C and D (50 +/- 95) than in patients with Dukes'A, B1 and B2 (25 +/- 54), p less than 0.07, but less significantly. The LAP score has at least the same reliability as the CEA values as a marker of stage in colorectal cancer patients.

Expression and functions of very late antigen 1 in inflammatory joint diseases.

In the human immune system, very late antigen 1 (VLA-1), a putative collagen receptor, is expressed on the surface of T lymphocytes that have undergone mitogenic or antigenic stimulation. A new VLA-1-specific monoclonal antibody, 1B3.1, was used to probe the expression and function of VLA-1 on T lymphocytes in patients with arthritis. Synovial mononuclear cells from the joints of patients with rheumatoid arthritis or other joint diseases contained 32.9 +/- 13.8% 1B3.1-positive cells (42.8 +/- 10.4% in patients with rheumatoid arthritis and 28 +/- 12.6% in non rheumatoid patients). In the peripheral blood, patients with active rheumatoid arthritis expressed VLA-1 on 11.7 +/- 6.0% of their mononuclear cells, compared to 1.9 +/- 1.5% in controls (P less than 0.001). Using dual fluorescence analysis, virtually all the 1B3.1-positive synovial cells were CD3+ T lymphocytes and included both CD4+ and CD8+ T cells. When 1B3.1-expressing synovial mononuclear cells or in vitro activated T lymphocytes were triggered with anti-CD3 antibodies, marked augmentation of their proliferation occurred if they were simultaneously cross-linked with mab 1B3.1. Collagen type IV, a putative ligand of VLA-1, also augmented T-cell proliferation to anti-CD3. The data suggest that the VLA-1 molecule could play an important role in the pathophysiology of arthritis by modulating T-cell activation in these diseases.

Carbamazepine metabolism in humans: effect of concurrent anticonvulsant therapy.

Free and total carbamazepine (CBZ) and carbamazepine-epoxide (CBZ-EP) plasma levels were obtained on 113 patients with epilepsy (18-61 years old) controlled on either monotherapy or coadministration with either phenobarbital (PB), phenytoin (PHT), valproic acid (VPA), or all three. A subset of patients were administered tetradeuterium labeled CBZ to evaluate the effects of autoinduction and coadministration of VPA on the kinetics of CBZ and its metabolite CBZ-EP. Polytherapy had variable effect on free and total CBZ plasma levels compared to monotherapy. Coadministered PHT (co-PHT), or all three anticonvulsants together (PHT, PB, and VPA: co-AEDs) decreased free and total CBZ plasma levels. No change was noted for coadministered VPA (co-VPA). Compared to monotherapy the free and total CBZ-EP levels increased with co-VPA, less with coadministered PB (co-PB), and no change with co-PHT or co-AEDs. Protein binding of CBZ and CBZ-EP was not affected by any antiepileptic drugs studied. The free and total CBZ-EP/CBZ ratio was tripled with co-VPA or co-AED's, and doubled with co-PHT or co-PB. Isotope labeling did not demonstrate any differences in half-life (t1/2), plasma clearance (Cl), or volume of distribution (Vd). Compared to naive controls, monotherapy and co-VPA decreased CBZ t1/2 by 50%, and more than doubled the CBZ Cl without a significant change in the Vd. Autoinduction is one explanation for these changes with chronic CBZ therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Leukocyte alkaline phosphatase and carcinoembryonic antigen in breast cancer patients. Influence of the treatment on the markers.

Leukocyte alkaline phosphatase (LAP) scores and carcinoembryonic antigen (CEA) levels were analyzed in 53 patients suffering from breast cancer. All patients underwent mastectomy and received adjuvant treatment, and all lived more than 5 years after diagnosis without metastatic disease. Thirty-three patients received adjuvant radiotherapy, and 20 patients received adjuvant chemotherapy. The median LAP score before radiotherapy was 117 +/- 48; two months after the beginning of radiotherapy this value was 175 +/- 71, being significantly higher than the original value (p less than 0.001), and one year after the beginning of radiotherapy it was 105 +/- 63, which approximated the normal scores. The median LAP score before chemotherapy was 138 +/- 69; two months after the beginning of chemotherapy it was 194 +/- 63, i.e. significantly higher than before chemotherapy (p less than 0.002), and one year after the beginning of chemotherapy it was 150 +/- 56. Median CEA levels before radiotherapy were 6.4 +/- 5.1 ng/ml; two months after the beginning of radiotherapy this value was 6.0 +/- 5.0 ng/ml; and one year later 7.4 +/- 6.2 ng/ml. Median CEA levels before chemotherapy were 8.1 +/- 12.0 ng/ml; two months after the beginning of chemotherapy 12.6 +/- 13.0 ng/ml (p less than 0.05) in comparison with the values before chemotherapy; and one year after the beginning of chemotherapy it was 8.6 +/- 5.4 ng/ml. We concluded that the LAP scores were influenced by adjuvant radio- or chemotherapy, and the CEA levels were influenced by chemotherapy.

A new scale for the assessment of functional status in Alzheimer's disease and related disorders.

Assessment of the functional competencies of patients with dementia is typically conducted in an indirect manner. Psychological tests of cognition or descriptions by relatives or other caregivers are often used to make judgments as to the patient's ability to adapt to the demands of the environment. However, these methods have built-in biases. The need for direct assessment of functional status was addressed by developing a standardized operational procedure to examine areas of functional competence which may become impaired in Alzheimer's disease and other related memory disorders. The resulting instrument has high interrater and test-retest reliabilities. Convergent validity is evidenced by significant correlations between the scale and established measures of functional status. Patients with Alzheimer's disease exhibited deficits in functional capacities relative to age-equivalent normal controls and to elderly patients with a primary major depression.

Leukocyte alkaline phosphatase and carcinoembryonic antigen in breast cancer patients: clinical correlation with the markers.

Leukocyte alkaline phosphatase (LAP) scores in peripheral blood and plasma carcinoembryonic antigen (CEA) levels were determined in 208 breast cancer patients with nonmetastatic disease. Patients were followed until clinical manifestations of metastases appeared. Then the LAP score and CEA level were analyzed in relation to the clinical appearance of metastases. Of the 208 patients studied, 58 developed metastases during the follow-up period. The LAP scores and CEA levels of this group of patients were compared to a control group of 60 breast cancer patients who did not develop metastases. Of the two markers, LAP score seems to be considerably more useful in detecting metastatic disease.

Changes in smell acuity induced by radiation exposure of the olfactory mucosa.

The effects of ionizing radiation on smell acuity were assessed in 12 patients in whom the olfactory mucosa was exposed to radiation in the course of treatment for nasopharyngeal carcinoma or pituitary adenoma. Olfactory detection thresholds for two odorants (amyl acetate and eugenol) were determined before the start of radiation therapy, within a week of termination of therapy, and 1, 3, and 6 months later. The results show clearly that smell acuity is profoundly affected by therapeutic irradiation. Thresholds had increased in all 12 patients by the end of treatment and were still high one month later. Varying degrees of recovery were noted in most patients three to six months after cessation of treatment. The fate of the sense of smell deserves more attention when considering the disability caused by irradiation to certain head and neck tumors.

Neurological sequelae of boxing.

Blunt trauma to the head results in acceleration of the brain within the skull. This takes 2 forms: linear or translational acceleration which produces focal lesions, and rotational acceleration which results in 'sheering stresses' with stretching of nerves and bridging veins. Deceleration of the brain within the skull occurs when the head strikes a stationary object (e.g. floor, ring post). Cerebrovascular events are not infrequently encountered. The most common vascular sequalae is the subdural haematoma, which is also the most frequent cause of death in boxers. Epidural bleeds rare, and are generally due to deceleration of the brain. Subarachnoid bleeds have been rarely reported, but, like intraparenchymal haemorrhages, they do occur. Sudden flexion/extension of the neck is suggested as the mechanism of the occasional brainstem haemorrhage reported in boxing. Thrombosis of the internal carotid artery can occur secondary to direct blows to the neck or stretching of the contralateral carotid artery. The best known sequalae of boxing is traumatic encephalopathy--the 'punch drunk' syndrome. This is most common in second-rate and slugging type fighters. Severity correlates with the length of a boxer's career and total number of bouts, with an incidence of approximately 18%. Three stages of clinical deterioration are seen, the encephalopathy may be progressive or may remain clinically stable at any level. The first stage consists of affective disturbances with psychiatric symptoms being most marked. During the second stage an accentuation of the psychiatric symptoms occurs and signs/symptoms of Parkinsonism develop. The final stage consists of a decrease in general cognitive function together with pyramidal tract disease. Generally 2 to 3 years elapse between the first and final stages. Neuropathological studies reveal abnormalities of the septum pellucidum, scarring of the cerebellar and cerebral cortices, and loss of pyramidal neurons in the substantia nigra with neurofibrillary tangles in the absence of senile plaques. A 'groggy state' can occur in some fighters with confusion, impaired active attention and alteration of consciousness. During this period the boxer is at greater risk to suffer brain injury as defensive reflexes are frequently lost. Other neurological syndromes have been reported in addition to the 'groggy state'. These include a midbrain syndrome, headaches and cervical spinal injuries. Additionally, boxing appears to be a significant risk factor for the development of meningiomas.(ABSTRACT TRUNCATED AT 400 WORDS)

[Surgical tactics in treating patients with extensive fibrocavernous pulmonary tuberculosis]. / O taktike khirurgicheskogo lecheniia bol'nykh s rasprostranennym fibrozno-kavernoznym tuberkulezom legkikh.

The principal idea of the method of surgery is the division of patients into two groups: a group of patients with a stable process and a group of patients with the disease in the stage of non-cupped exacerbation. When using any surgical interventions one should follow the principle of maximum preservation of the functioning lung tissue, the surgery being performed in the size of destructive changes in the lungs. In a unilateral cavernous injury resection of the lung or pneumonectomy was the main method of surgery. In the treatment of patients with bilateral caverns the main line of the surgical tactics is the planned bilateral surgical treatment, individual selection of the optimal combination of different operations, division of the surgical treatment into steps and choice of their sequence.