Effect of long-term lead exposure on hematology, blood biochemistry, and growth curves in monkeys

A total of 90 monkeys (Macaca fascicularis), comprising four study cohorts born over a seven-year period, were hand reared and dosed orally with lead or vehicle according to one of several protocols, in most cases from birth to 9-14 years. Blood lead concentrations of lead-exposed groups ranged from 10 to 90 micrograms/dl depending on dose and age. Routine hematology and blood biochemistry analyses were performed regularly. Comparison of treated groups at various ages to the appropriate control group revealed no strong indication of lead-related effects. In addition, body weight increase was modeled from days 30-3500 of age in subset of this larger group, including 52 monkeys exposed to vehicle or lead during development according to one of four regimens: vehicle, lead from birth onward, lead to 400 days of age, or lead beginning at 300 days of age. No effect of lead on body weight was found. These results suggest that lead exposure beginning early in life and continuing for as long as 14 years resulted in no overt toxicity, as measured by these parameters.     

Motor reconnection between the damaged cervical cord and the denervated biceps muscle using an autologous peripheral nerve segment in the adult marmoset]

Our research group is studying, in the primate (marmoset), the conditions of an anatomical and functional reconstruction of the spinal cord and of its motor connections, following a focal spinal lesion. In this attempt to repair the damaged neuronal circuitry, we used long segments of autologous peripheral nerves joining the injured cervical spinal cord to an aneural region of the denervated biceps brachialis muscle (7 marmosets) or to the musculocutaneous nerve (6 marmosets). After retrograde tracing (HRP) and histochemical studies of the muscle, we found that a great number of neurons, located mostly in the ventral part of the grey matter extended axons into the peripheral nerve graft. Some of these labelled neurons were motoneurons, which could established functionnal neuromuscular junctions. The muscle regeneration was effective but slower than already known in rat studies.     

Effect of dopamine receptor antagonists on cocaine subjective effects: a naturalistic case study

Schizophrenic patients on neuroleptic medications abuse cocaine and report cocaine-induced euphoria. This study was undertaken to provide better clinical characterization of these phenomena by administering the POMS and a custom-designed questionnaire. A group of heavy cocaine users who were not mentally ill served as the control group. The results clearly suggest that schizophrenic patients report cocaine-induced euphoria and post-use craving despite being treated with therapeutic doses of haloperidol or fluphenazine. The responses of the control group were similar to that of the schizophrenic group except that the latter subjects reported a greater degree of anxiety. These results suggest that blockade of D2 receptors is not sufficient to block cocaine-induced subjective effects in humans.     

Cancer incidence and mortality: the priority of screening frequency and population coverage

In addition to the usual measures of screening-test performance, it is important to consider testing frequency when evaluating a screening program. Data on which to base recommendations for the timing of screening tests are urgently needed. For example, in the cases of cervical and colon cancer, when the target is a precursor lesion, research indicates that less frequent screening may be appropriate. This finding may not apply, however, to screening for breast cancer by mammography, which requires currently recommended intervals for the early detection of malignancies. Resources now allocated to breast cancer might more effectively be applied to the construction of tests that would permit longer intervals between screenings. To achieve the National Cancer Institute's goal of reducing cancer mortality in the United States by the year 2000, it will be important to review the balance between population coverage and individual screening for each cancer and to emphasize prevention strategies that maximize population coverage while minimizing expenditures.     

Weaning from mechanical ventilation

For the ventilator-dependent patient, weaning should be accomplished by withdrawing support safely, efficaciously, and efficiently. Success depends largely on physiologic determinants of respiratory system function, avoidance of ventilator-associated complications, and attention to patient readiness. Recent clinical trials, predictors of weaning, current techniques of weaning, the concept of reloading the respiratory pump, and determinants of ventilator dependency are all discussed.     

Metabotropic glutamate receptors contribute to the induction of long-term depression in the CA1 region of the hippocampus

Long-term depression of synaptic transmission was induced following the prior induction of long-term potentiation in the CA1 region of rat hippocampal slices. We show that the induction of this form of synaptic depression can be prevented by (+)-alpha-methyl-4-carboxyphenylglycine, a selective antagonist of metabotropic glutamate receptors.     

Cellular and molecular regulation of serotonin N-acetyltransferase activity in chicken retinal photoreceptors

Serotonin N-acetyltransferase (AA-NAT; arylalkylamine N-acetyltransferase; EC 2.3.1.87) is the penultimate enzyme in melatonin synthesis and large changes in the activity of this enzyme appear to regulate the rhythm in melatonin synthesis. Recent advances have made it possible to study the mRNA encoding chicken AA-NAT, which has only been detected in the retina and pineal gland. Within the retina, AA-NAT mRNA is expressed primarily in photoreceptors. The levels of chicken retinal AA-NAT mRNA and activity exhibit 24-hour rhythms with peaks at night. These rhythms appear to reflect circadian clock control of AA-NAT mRNA abundance and independent effects of light and darkness on both mRNA levels and enzyme activity. The effects of darkness and light may occur through alterations in cAMP-dependent protein phosphorylation, which increases AA-NAT activity in photoreceptor cell cultures. The cAMP-dependent increase of AA-NAT enzyme activity reflects, at least in part, increased mRNA levels and inhibition of enzyme inactivation by a posttranslational mechanism. This review discusses a hypothetical model for the cellular and molecular regulation of AA-NAT activity by circadian oscillators and light in chicken retinal photoreceptor cells.     

Reanalysis of the National Institute of Mental Health Treatment of Depression Collaborative Research Program General Effectiveness Report

The National Institute of Mental Health (NIMH) Treatment of Depression Collaborative Research Program General Effectiveness Report statistical analyses are criticized. Their analyses, which fostered the belief that criticized. Their analyses, which fostered the belief that the active treatments were indistinguishable, were compromised by an inappropriately stringent level of significance with regard to both heterogeneity of slope and pairwise group differences. Once slope heterogeneity is detected, the Johnson-Neyman technique is more appropriate than arbitrary sample subdivision. All of these tactics lowered power substantially. Our reanalysis indicates a reasonable ordering for the treatments with medication superior to the psychotherapies and the psychotherapies somewhat superior to placebo. These effects are particularly marked among the more symptomatic and impaired patients. The lack of dosage by severity analyses renders the severity findings ambiguous. Scientific and public health implications are discussed.     

Factors affecting bone graft incorporation

Successful graft incorporation requires that an appropriate match be made among the biologic activity of a bone graft, the condition of the perigraft environment, and the mechanical environment. The authors have studied, in a wide variety of animal models, the factors that affect the main components of bone graft incorporation: revascularization, new bone formation, and host-graft union. The principal determinant of the rate, pattern, and amount of revascularization is the presence or absence of a vascular pedicle. The nonvascularized bone graft is entirely dependent on the surrounding tissue for its revascularization, which results in a noticeable delay in vessel ingrowth. The principal determinant of the rate and amount of new bone formation on, in, or about a bone graft is the presence or absence of living, histocompatible, committed bone-forming cells. When living cells are not part of the graft at the time of implantation, the cells that form new bone are derived from host tissues, and new bone formation is delayed. The principal determinants of host-graft union are stability of the construct and contact between host bone and the graft. Factors that slow or inhibit all of these processes are reduction of the biologic activity of the graft by freezing or some other treatment, histocompatibility antigen disparities between donor and recipient, mechanical instability between the graft and the perigraft environment, and local and systemic interference with the biologic activity of the graft and surrounding tissue, for example, by irradiation or the administration of cisplatin. The task of the clinician who does a bone grafting procedure is to choose the right graft or combination of grafts for the biologic and mechanical environment into which the graft will be placed.