Technology and effect: HIV/AIDS testing in Brazil.

Contemporary techno-scientific and medical developments are restructuring social interactions and the very processes by which individual subjectivity is formed. This essay elaborates on the experiential and ethical impact of such transformations from the perspective of people who, in ordinary and unexpected ways, act science and technology out. We carried out ethnographic research in an HIV/AIDS Testing and Counseling Center (CTA) in northeastern Brazil, combining participant observation with epidemiological analyses and clinical survey. We found a high demand for free testing by low-risk clients, largely working and middle class, experiencing anxiety and complaining of AIDS-like symptoms. Most of the clients were sero-negative and many returned for a second and third testing. We understand this to be a new techno-cultural phenomenon and call it imaginary AIDS. Throughout this essay, we describe CTA's routine practices, place these practices in historical, political, economic and cross-cultural perspective, and analyze the subjective data we collected from the clients of our pilot study. We explore how clinical epidemiological expertise and HIV testing technology are integrated into new forms of bio-politics aimed at specific marketable and disease-free populations, and on the affective absorption of bio-technical truth and the engendering of a technoneurosis in this testing center.

Military and civilian penetrating eye trauma: anesthetic implications.

In 20th century warfare, wounds from fragmentation weapons have become the number 1 cause of military hospital admissions during combat. Specifically, grenades, landmines, mortars, and artillery weapons have replaced guns and bullets. Consequently, penetrating eye injuries and maxillofacial injuries in the military have escalated dramatically. In the civilian sector, pipe bombs, explosive bottles used in gang warfare, and terrorist bombs, which are all fragmentation weapons, have generated new studies in the care of patients with penetrating eye injury. This change in the wounding pattern is, documented internationally in military-medical literature and in civilian-medical literature of relief agencies such as the International Committee of the Red Cross and the Red Crescent. The anesthetic management of open eye injuries has been a running controversy for 40 years in terms of the use of muscle relaxants. Nondepolarizing agents carry the risk of aspiration and increased intraocular pressure when trauma patients are intubated prematurely during rapid-sequence induction for "full stomachs." Succinylcholine would be the logical relaxant of choice for a rapid-sequence induction, but succinylcholine raises intraocular pressure. In many cases, the literature specifically contraindicates succinylcholine in the open eye injury for fear of extruding the content of the eye. A review of the vital assessment for the patient with a penetrating eye injury, as well as a comparative analysis of the literature, is presented. The conclusion favors pretreatment with a nondepolarizing agent and the use of succinylcholine during rapid-sequence induction. The eye injury itself is not the primary concern of this article. The primary concern is that open eye injuries serve as hallmarks for for more dangerous injuries. Penetrating open eye injuries merit extensive clinical assessment that can be life saving.

Penetrating eye injury in war.

The percentage of penetrating eye injuries in war has increased significantly in this century compared with the total number of combat injuries. With the increasing use of fragmentation weapons and possibly laser weapons on the battle-field in the future, the rate of eye injuries may exceed the 13% of the total military injuries found in Operations Desert Storm/Shield. During the Iran-Iraq War (1980-1988), eye injuries revealed that retained foreign bodies and posterior segment injuries have an improved prognosis in future military ophthalmic surgery as a result of modern diagnostic and treatment modalities. Compared with the increasing penetrating eye injuries on the battlefield, advances in ophthalmic surgery are insignificant. Eye armor, such as visors that flip up and down and protect the eyes from laser injury, needs to be developed. Similar eye protection is being developed in civilian sportswear. Penetrating eye injury in the civilian sector is becoming much closer to the military model and is now comparable for several reasons.

Antidepressant action of sulpiride. Results of a placebo-controlled double-blind trial.

The purpose of this multicenter, randomized, double-blind, placebo-controlled parallel-group comparative study was to prove the efficacy and tolerance of sulpiride (150-300 mg) against placebo in mild to moderate depressive syndrome. The primary criterion of efficacy was the course of the HAMD total score from day 1 to day 42, compared between the two treatment groups. The duration of the treatment was six weeks, preceded by a one-week placebo run-in phase. The HAMD, CGI and KUSTA scores were determined, the tolerance assessed, and the laboratory parameters and serum prolactin levels determined before, during and at the end of the trial. 177 outpatients aged from 18 to 70 years with mild to moderate depressive syndrome (ICD-10: F32.0, F32.1, F33.0, F33.1) and a score of 18-27 points on the 21-item HAMD scale were randomized, 171 of whom (sulpiride: n=83; placebo: n=88) were included in the intention-to-treat analysis. All the baseline data recorded for the two groups displayed comparable values. The decrease of the HAMD score between day 1 and day 42 yielded a difference of 2.5 points in favour of the sulpiride group. This difference is statistically significant (p = 0.0007). The evaluations of the cases treated for at least 14 days or for 42 days (per protocol) showed consistent values. The analysis of the CGI values showed similarly distinct and clinically relevant differences for sulpiride in comparison with placebo. The evaluation of the KUSTA scores yielded mostly comparable values for the two groups. Adverse events occurred with about the same type and frequency in both groups, with severe adverse events occurring only in two placebo patients. The laboratory parameters revealed no significant differences between the treatment groups, with the exception of prolactin which moderately exceeded the range of normal in 50% of the patients treated with sulpiride. This trial proved that sulpiride is effective and well-tolerated when given in a mean dose of 181 mg per day for mild and moderate depression.

Environmental variables and mobility performance in adults with low vision.

BACKGROUND: Surveys and empirical studies of visually impaired (VI) persons suggest that avoidance of objects while walking may depend on type of vision loss and be influenced by light level, object contrast, and object type. METHODS: Mobility performance in 88 VI adults was assessed on an indoor obstacle course under photopic and mesopic lighting conditions. Subjects were divided into three categories: primarily an acuity loss, primarily a peripheral field restriction, and a combination of the two. Performance measures were time to walk the course and total number of contacts with objects in the course. RESULTS: Decreasing light level from photopic to mesopic resulted in a significant increase (roughly double) in the time required to complete the course and in the total number of contacts, regardless of type of vision loss. Under photopic illumination, subjects with acuity loss took less time on average to complete the course and contacted fewer objects than the other two groups. At mesopic levels, acuity loss subjects performed better than those in the other categories. Low contrast obstacles were contacted more frequently than high contrast ones at both light levels. Finally, floor level walk-around objects were contacted significantly less often than either step-over or head level objects, regardless of type of vision loss and light level. CONCLUSIONS: The ability of VI persons to avoid obstacles is significantly impaired under mesopic illumination. Object contrast and location are significant factors in determining the success of VI persons in avoiding obstacles in the travel path.

Absorption behavior of sulpiride described using Weibull functions.

Deconvolution absorption profiles of oral sulpiride formulations were calculated from plasma concentration-time data obtained in an open, 3-period study with a crossover of the 2 oral formulations in 12 healthy volunteers following single intravenous (100 mg) and oral (2 x 50 mg capsules, 200 mg tablets) application of sulpiride. A model based on 2 Weibull-functions, and applied using NONMEM, described the complex absorption profiles more satisfactorily than a first order absorption model or a model based on a single Weibull-function.

Pharmacokinetics of the analgesic o-carbamoylphenoxyacetic acid.

The pharmacokinetics of o-carbamoylphenoxyacetic acid was studied in 9 male healthy subjects following a single i.m. administration of 1000 mg of this compound in form of its sodium salt. Venous blood specimens were drawn up to the 10th h p.a. and the plasma concentration of o-carbamoylphenoxyacetic acid and its metabolite salicylamide were determined using a specific HPLC-assay. Following injection, o-carbamoylphenoxyacetic acid was rapidly distributed in the body since the maximal plasma concentration occurred within 0.37 +/- 0.08 h and was determined with 23.5 +/- 7.51 micrograms/ml in mean. In the following, the plasma concentration declined rapidly as well according to the mean terminal elimination half-life of 0.93 +/- 0.23 h. By contrast, plasma concentration of the metabolite salicylamide was comparatively low. Mean maximal plasma concentration amounted to only 0.18 +/- 0.03 microgram/ml and the peak concentration occurred 1.08 +/- 0.43 h after injection. The mean of the individual areas under the plasma concentration time profiles AUC(O-t) was 30.2 +/- 3.96 micrograms x h/ml for the parent compound and 0.69 +/- 0.14 microgram x h/ml for the metabolite. The relative mass portion of salicylamide vs o-carbamoylphenoxyacetic acid in systemic circulation was estimated with 0.008 comparing mean Cmax and with 0.023 comparing the mean areas AUC(O-t). A possible interpretation of these findings might be that a relatively stable ether bond exists in o-carbamoylphenoxyacetic acid which has to be cleaved during the formation of salicylamide. Due to the moderate rate of metabolic conversion, only minor quantities of salicylamide appeared in the systemic circulation. Furthermore, its peak concentration occurred at a time 2-3 times later than that of the parent compound.

Induction-dependent and lineage-dependent models for cell diversification are mutually exclusive.

The purpose of this brief review is to put into perspective just how little is known about the mechanisms that control the assembly of the differentiation program of any cell type. Any number of "trivial" changes in the microenvironment of a Friend erythroleukemic or of a neuroblastoma cell induces both covertly differentiated cells to reveal their lineage affiliations. Demethylating molecules, BudR, retinoic acid, cAMP, butyrate or other "inducing molecules" do not, however, transform the descendents of the neuroblastoma cell into a Hb- synthesizing cell or vice versa. For thousands of generations both of these immortialized lines transmit to their daughters their unique, lineage-dependent differentiation programs with great fidelity. The stability of the inherited transcription complex that is ultimately responsible for this covert differentiation program of these cell lines--or of normal precursor cells--is awesome. Clearly, with these immortalized cells as with normal chick blastodisc cells, the cell's microenvironment plays a major role in permitting or blocking the expression of the cell's inherited differentiation program. But the program itself must be generated by intracellular mechanisms and must be inherited; its assembly is not dependent upon inductive events initiated by exogenous molecules.

Quantal and proliferative cell cycles: how lineages generate cell diversity and maintain fidelity.

There are no known differences between the mechanisms that generate diverse differentiation programs in a mosaic embryo such as Caenorhabdites elegans or in a regulative embryo such as a chick. Transit through an invariant sequence of compartments in a lineage is obligatory for a given precursor cell 1) to inherit its differentiation program from its mother, and 2) to transmit to its daughters, by way of a predetermined binary decision, a new differentiation program. The inheritability of a differentiation program must be encoded in a structural molecule. We postulate that during an S period of a quantal cell cycle, chromosomal structures are so altered that a network of genes that could not be transcribed in the mother becomes available for transcription in the daughters. We do not view as a likely possibility the traditional notion that cell-cell or cell-matrix interactions instruct or commit blank, naive cells to transform into cells with unique differentiation programs. From this perspective, we have initiated experiments to determine the minimal rounds of DNA synthesis, following fertilization, that are required to generate founder cells for several major lineages in the chick. Somewhere between the 15th and 18th generations after fertilization erythrogenic hematocytoblasts that are cytokeratin-positive and vimentin- and hemoglobin-negative undergo a quantal cell cycle. Their daughters are cytokeratin-negative and vimentin- and hemoglobin-positive. DNA synthesis, but not cytokinesis, is an obligatory requirement for this switch in differentiation programs. Essentially similar findings are presented for cells in the cardiogenic, neurogenic, melanogenic, and endothelial lineages. There is no evidence that cell-cell or cell-matrix interactions are required for this diversification. Such interactions, however, may be required for the large number of proliferative cell cycles within particular compartments of particular lineages that are characteristic of all growing or expanding systems. With respect to classical "CFU cells" it is of interest that definitive white blood cells have not yet been identified in these cultures. Lastly, the high ratio of primitive red blood cells to non-red blood cells in the first 40 hours of culture is consistent with the notion that the majority of all cells present in the blastodisc at these early stages are in fact already committed to a unipotent erythrogenic lineage [5, 18, 23, 44, 45]. The issue of changing ratios of cells within compartments of a lineage, as well as of cells in different lineages, is much neglected in consideration of (a) normal embryogenesis, (b) cell-renewal in mature organisms and, particularly,

Effects of 12-O-tetradecanoylphorbol-13-acetate on the differentiation of avian melanocytes.

12-O-Tetradecanoylphorbol-13-acetate (TPA) has been reported to inhibit and/or delay the terminal differentiation of a variety of cell types. More recently, TPA has been reported to enhance melanogenesis in cultured human melanoma cells. This study focuses on the effect of TPA on the differentiation of normal avian melanocytes. TPA blocked melanogenesis in normal replicating presumptive melanoblasts, as well as in replicating pigmented melanocytes derived from the neural crest, the retinal pigment epithelium, and the pecten oculi. These normal embryonic cells not only failed to synthesize melanin but also failed to assemble premelanosomes and to assume either the characteristic dendritic processes of normal trunk melanocytes or the epithelioid morphology of the normal retinal pigment epithelial cell. This inhibition was remarkably reversible. Following removal of TPA, the previously blocked neural crest cells became pigmented and formed their characteristic dendritic processes, whereas the previously blocked retinal cells formed a pigmented epithelium. The effect of TPA on these normal cells was dependent on duration of exposure and degree of differentiation of the cells at the time of exposure. TPA induced the formation of elongated neurite-like processes in the amelanotic neural crest cells which differed in their cytoskeletal structure from the dendritic processes of normal trunk melanocytes. These TPA-blocked pigment cells with elongated processes bear a striking morphological resemblance to presumptive myoblasts, chondroblasts, and fibroblasts treated with the tumor promoter.