Fueguian cranial morphology: the adaptation to a cold, harsh environment.

Craniometric data from the three extinct tribes that inhabited Tierra del Fuego (Selk'nam, Yámana, and Kawéskar) were gathered following Howell's measurement technique. We studied 180 skulls preserved at thirteen different institutions. Analysis of variance (ANOVA) between groups showed that morphological similarities among Fueguian groups are far more important than some differences between marine (Yámana and Kawéskar) and terrestrial (Selk'nam) groups. A principal component analysis (PCA) generated from the correlation matrix shows that Fueguians fall as outliers with respect to the typical Mongoloid morphology. In addition, a UPGMA tree generated from a squared Euclidean distance matrix indicates that Fueguian groups have a morphological pattern that is very distinct from that of other present-day Amerindian groups, with the exception of the Eskimos. One of the variables that contributes substantially to the differentiation of Eskimos and Fueguians is the nasal height. This suggests that nasal morphology in both groups could be a response to adaptive pressures related to the cold environment. However, other morphological particularities of Fueguian skulls, such as craniofacial robustness and variables of craniofacial width, can be attributed to a large masticatory stress. As a whole, the morphological features of Fueguian groups can be regarded as a general adaptive response to a very harsh environment, along with the retention of some plesiomorphic features. Assuming that the initial entry in Tierra de Fuego took place around 10,000 years BP, before the disappearance of the last land bridges in the Magellan Straits, then this adaptation might have arisen in a relatively short period, hastened by the extreme environmental conditions.

mtDNA analysis in ancient Nubians supports the existence of gene flow between sub-Sahara and North Africa in the Nile Valley.

The Hpal (np3,592) mitochondrial DNA marker is a selectively neutral mutation that is very common in sub-Saharan Africa and is almost absent in North African and European populations. It has been screened in a Meroitic sample from ancient Nubia through PCR amplification and posterior enzyme digestion, to evaluate the sub-Saharan genetic influences in this population. From 29 individuals analysed, only 15 yield positive amplifications, four of them (26.7%) displaying the sub-Saharan African marker. Hpa 1 (np3,592) marker is present in the sub-Saharan populations at a frequency of 68.7 on average. Thus, the frequency of genes from this area in the Merotic Nubian population can be estimated at around 39% (with a confidence interval from 22% to 55%). The frequency obtained fits in a south-north decreasing gradient of Hpa I (np3,592) along the African continent. Results suggest that morphological changes observed historically in the Nubian populations are more likely to be due to the existence of south-north gene flow through the Nile Valley than to in-situ evolution.

Phytolith analysis on dental calculus, enamel surface, and burial soil: information about diet and paleoenvironment.

Silica phytoliths (microscopic remains originating in plant tissues) have been identified on the enamel surface and dental calculus of a sample of teeth selected from well preserved skeletons from a Late Roman necropolis in Tarragona (Spain). Phytoliths were observed by scanning electron microscopy (SEM) and their siliceous nature was confirmed by X-ray microanalysis. The phytoliths were compared to those of soil samples from both the areas of the tombs corresponding to the abdomen and the periphery of the skeletons, and were classified taxonomically by comparison with a large collection of silica particles from modern plants in the Mediterranean area. Most of the phytoliths identified on the enamel and the dental calculus belong to the family of Poaceae, while the phytoliths from the abdominal area belong to Poaceae, Leguminosae, Cyperaceae, and Chenopodiaceae. Results are concordant with archaeological, ecological, and historical data from the same site, and with the human Mediterranean diet. If done properly, the study of phytoliths can provide direct information about the vegetable diet of past human populations, and could be applied to the study of human fossils.

Cranial variation in the Iberian Peninsula and the Balearic Islands: inferences about the history of the population.

A multivariate analysis of four prehistoric and nine historic populations from the Iberian Peninsula and Balearic Islands with large sample sizes (n > 30 individuals for the neurocranium and n > 15 for the facial skeleton) is presented, considering 874 male and 557 female skulls and using 20 craniometric measurements. Cluster analyses have been undertaken using the squared Euclidean distance as a measure of proximity and the average linkage between groups (UPGMA), and neighbor-joining algorithms as a branching method, and a bootstrap analysis was used to assess the robustness of the clustering topology. The study was complemented with a principal coordinate analysis and with the application of the Mantel test to measure the degree of correspondence between the information furnished by the female and the male samples. The analyses show that the main source of morphometric variability in the Iberian Peninsula is the Basque population. The second source of variation is provided by two populations (Muslims and Jews), different from the rest from an archaeological and cultural point of view, and can probably be attributed to influences from sub-Saharan Africa. The massive deportations of the Jews in 1492 and of the Moors between the 15th and 17th centuries may have erased this source of variability from the present population of the Iberian Peninsula. The remaining studied populations, including samples from Castile, Cantabria, Andalusia, Catalonia and Balearic Islands, are grouped together, showing a notable morphological homogeneity, despite their temporal and geographic heterogeneity. These results are in general agreement with those obtained in synthetic maps, by analyzing multiple genetic markers. In such studies, the Basque population is described as the main source of genetic variability, not only in the Iberian Peninsula, but also in Western Europe.

Comparative evaluation of zinc sulfadiazine and silver sulfadiazine in burn wound infection.

One percent silver sulfadiazine has been commonly used as a topical antimicrobial agent after a burn injury. Incidence of burn wound colonization by Staphylococcus aureus in patients treated with silver sulfadiazine has spurred research for other agents. A topical preparation that contains zinc and sulfadiazine (Zad-G) was evaluated for in vitro antibacterial spectrum and in vivo efficacy. Muscle biopsy specimens of rats treated with Zad-G appear to have fewer colonies of S. aureus than groups treated with silver sulfadiazine. Topical therapy with Zad-G for patients with burns was comfortable, reduced wound infection, and was comparable to therapy with silver sulfadiazine. A topical Zad-G preparation that contains zinc sulfadiazine appears to be an effective alternative to silver sulfadiazine in the treatment of burn wounds.

A comprehensive approach to drug-free schools and communities.

A comprehensive approach to developing and maintaining drug-free schools and communities is discussed. Five sequential phases, needs assessment, planning, implementation, evaluation, and dissemination, are described. An effective implementation program meets the needs of students at various stages of drug use and abuse. Prevention strategies are effective with students who have only experimented or never used drugs, while early intervention strategies are most effective for students who have a more regular use pattern. Chemically dependent students need referral for treatment at a community social agency. After treatment and rehabilitation, returning to a supportive aftercare school program proves most effective. The approach described in this article advocates a team effort including well-trained school core teams collaborating with parents and community representatives from law enforcement, social agencies, business, religious groups, and the media.

Combined topical use of silver sulfadiazine and antibiotics as a possible solution to bacterial resistance in burn wounds.

The superior efficacy of quinolones (norfloxacin, pefloxacin, and enoxacin) in controlling burn wound infections signals the discovery of new topical agents. However, there are a few reports on the emergence of resistant mutants to quinolones. Since attempts to develop AgSD resistant strains in vitro were unsuccessful and the emergence of AgSD resistance in vivo is a rare occurrence, we decided to investigate if the combined use of AgSD with other effective antibiotics, especially quinolones, would minimize the development of resistant bacteria. Our in vitro results indicate that when Ps. aeruginosa cultures were serially transferred 10 times through subinhibitory concentrations of norfloxacin, pefloxacin, etc., the MIC increased 40 times while when the cultures were passed through a combination of AgSD and these quinolones, the MIC of quinolones increased only tenfold. In vivo, when burned mice infected with either AgSD sensitive or resistant Ps. aeruginosa strains were treated with a topical cream containing 10mM silver sulfadiazine and 5mM norfloxacin or 5mM pefloxacin, the mortality was much lower than that of 10mM silver sulfadiazine alone or 5mM quinolones alone. Thus, combined use of silver sulfadiazine and quinolones appears to diminish the ability of Ps. aeruginosa strains to form resistant mutants. Furthermore, when the combination is used as a topical agent in burn wounds, lesser amounts of the individual drug are needed to control infection thereby reducing the toxic effects, if any, associated with these drugs. This combination does not in any way interfere with the antifungal or antibacterial properties of these individual drugs.

Control of prosthetic bacterial infection: evaluation of an easily incorporated, tightly bound, silver antibiotic PTFE graft.

Despite the use of prophylactic antibiotics in vascular surgery, prosthetic infection rate remains 2-5%. Antibiotics bound to vascular prostheses can control experimentally induced infection but prolonged antibacterial activity has not been achieved. This study evaluates the in vivo efficacy and antibiotic retention of an easily prepared silver-antibiotic prosthesis. Prostheses were prepared by combining silver with oxacillin or amikacin using an organic solvent. After evaporation of the solvent, the graft was left impregnated with the antibiotic complex. In vivo retention studies were performed by implanting PTFE 110Ag-oxacillin prostheses in four canine abdominal aortas. When prostheses were explanted at 1 week, mean antibiotic retention was found to be 20% of original activity, higher than the mean inhibitory concentration for Staphylococcus aureus. In three groups of five dogs, 20 X 7-mm prostheses of PTFE alone, PTFE silver-oxacillin, or PTFE silver-amikacin were implanted in the abdominal aorta and the grafts were inoculated with 10(7) S. aureus of a known bacteriophage type, in a closed retroperitoneal pocket. The animals were sacrificed at 1 week and the prostheses were excised for quantitative bacterial culture. PFTE silver-oxacillin, and PTFE silver-amikacin prostheses had 1.7 X 10(2) and 2.0 X 10(2) colonies, respectively, significantly less (P less than 0.05) than controls (1.3 X 10(6) colonies). These data suggest that antibiotic prostheses can be easily prepared without binding agents. They retain the bound antibiotic for a prolonged period and are effective in reducing graft infection in a stringent direct contamination model.

PTFE graft treated with silver norfloxacin (AgNF): drug retention and resistance to bacterial challenge.

Norfloxacin (NF) and silver norfloxacin (AgNF) were used to coat polytetrafluoroethylene (PTFE) vascular prostheses by using triododecylmethylammonium chloride as a cationic surfactant. The relative retention of the drug on the graft after subjecting it to the biological environment for 3 weeks and antibacterial activity against coagulase-positive Staphylococcus aureus and Escherichia coli were determined. In addition, the ability of AgNF-coated PTFE grafts to sterilize perigraft tissue after mixed bacterial contamination was studied and compared with control PTFE grafts in 10 dogs. At the end of 21 days, 15 and 18% of AgNF were retained on the grafts tested in in vitro and in vivo experiments, respectively. During the same time AgNF-coated grafts from in vitro experiments exhibited significant antibacterial activity (25 mm zone of inhibition (z.i.)), but antibacterial activity was negligible (10 mm z.i.) in the grafts from in vivo experiments. NF retention on the grafts could not be determined because of spectral interference by blood. The antibacterial activity of NF-coated grafts significantly declined after 24 hr in in vivo experiments, hence further evaluation of NF-coated grafts was not done. Seven perigraft sites surrounding AgNF-coated grafts were sterile, but only one perigraft site surrounding control grafts was sterile (P less than 0.05). Cultures from six of nine perigraft infections surrounding control grafts yielded heavy bacterial growth. There was only one wound infection at the site of AgNF graft while there were seven severe wound infections at control graft sites. AgNF-coated grafts exhibited prolonged antibacterial activity compared to NF-coated grafts and offered significant protection against infection from local bacterial contamination.

A new method for the direct incorporation of antibiotic in prosthetic vascular grafts.

A procedure for the bonding of antibacterial agents directly to prosthetic vascular grafts has been developed. This method does not involve the use of carriers or surfactants which may cause local toxicity or thrombogenesis. Using this procedure, antibiotics can be bonded to the graft alone or in combination with a metal, such as silver. Incorporation of silver along with the antibiotic enhances the antibacterial activity and prolongs retention of the antibiotics in the prosthetic grafts. Silver mediated bonding appears to release the antibiotic biphasically. In the initial phase (40 to 50 per cent), the drug is rapidly released and, in the second phase, the rest is diffused gradually enabling the graft to retain antibacterial activity for a longer period of time.

Response of varicella zoster virus and herpes zoster to silver sulfadiazine.

The addition of silver sulfadiazine to cultures of varicella zoster virus resulted in inactivation of the viral infectivity. At a concentration of 10 micrograms/ml or higher the virus was inactivated after thirty minutes exposure at 37 degrees C. Forty-two patients with herpes zoster were treated topically with 1 percent silver sulfadiazine cream applied four times a day. All patients experienced complete drying of vesicles, marked reduction erythema and edema, and striking elimination of pain and burning sensation within twenty-four to seventy-two hours. The sooner the treatment began after the onset of symptoms, the more dramatic was the response. Postherpetic neuralgia was either mild or did not occur. Signs of local, systemic, or laboratory-documented toxicity were not observed.

Synergistic action of silver sulfadiazine and sodium piperacillin on resistant Pseudomonas aeruginosa in vitro and in experimental burn wound infections.

Silver sulfadiazine-resistant organisms are arising at an irregular rate and may eventually interfere with wound management. To counter this problem several new antibacterial agents were tested in combination with silver sulfadiazine. Only sodium piperacillin (Pipracil, Lederle) exhibited synergism with silver sulfadiazine both in vitro (against various species of organisms) and in burned animals. The MIC of AgSD and Pipracil was 50 nmole/ml and 250 nmole/ml, respectively, but a combination of 6 nmole/ml of AgSD and 7.5 nmole/ml of Pipracil inhibited the growth of Pseudomonas aeruginosa. In burned mice infected with either AgSD-resistant or sensitive strains, the mortality in groups receiving combinations of topical Pipracil and silver sulfadiazine was 0-10%; in contrast, treatment with Pipracil or silver sulfadiazine alone resulted in much higher mortality. Thus it would appear that a combination of silver sulfadiazine and Pipracil, each of which have long been used in patients topically and parenterally, may prove valuable in patients with burn wound infections related to or caused by organisms resistant to silver sulfadiazine.

Simple methods for direct antibiotic protection of synthetic vascular grafts.

Two simple methods for direct antibacterial protection of synthetic vascular grafts were investigated. In the first protocol the highly protein-bound antibiotics nafcillin (90% protein bound), cefazolin (80%), and cefamandole (70%) were added directly to preclotting blood. Knitted Dacron grafts preclotted in the presence of one of these drugs absorbed significant amounts. Although at high concentrations these antibiotics exhibited anticoagulant effects, significant antibacterial protection was obtained at lower antibiotic levels. Washing treated grafts for 6 hours failed to eliminate the antibacterial activity. Antibiotics remained on the grafts for at least 96 hours. In the second protocol knitted Dacron grafts were soaked in a suspension of silver-pefloxacin, a silver-nalidixic acid analogue with intense antistaphylococcic activity. Using 110Ag-labeled complexes, significant antibiotic activity was documented on the graft after 19 days of washing. Four nafcillin-treated prostheses, six silver-pefloxacin-coated grafts, and 11 control grafts were interposed in the infrarenal aorta of dogs and immediately challenged with an intravenous infusion of 1 X 10(7) Staphylococcus aureus. None of the four nafcillin-treated grafts was infected at 3 weeks. One of the six silver-pefloxacin-coated grafts grew staphylococci, and 9 of 11 controls had positive graft cultures for Staphylococcus when harvested. These studies suggest that prosthetic grafts can be simply coated at the time of implantation with antibiotics selected for appropriate binding and antibacterial characteristics to obtain an infection-resistant prosthesis.

Control of burn wound infections by pefloxacin and its silver derivative.

As might be anticipated, strains of Pseudomonas aeruginosa resistant to silver sulfadiazine have appeared. We have found an analogue of nalidixic acid (pefloxacin) which, along with its silver derivative, is highly effective against these resistant strains. In vitro the minimal inhibitory concentrations are 10 to 20 times lower than that of silver sulfadiazine against bacteria. In burned mice and rats infected with silver sulfadiazine resistant pseudomonas strains, mortality in groups receiving topical therapy with pefloxacin and silver pefloxacin is about 10 per cent compared to 80 per cent with silver sulfadiazine (100 per cent in untreated controls). There is little systemic absorption of pefloxacin and no absorption of silver from topical treatment. In addition, silver pefloxacin exhibits higher antifungal activity in vitro.

Norfloxacin and silver norfloxacin in the treatment of Pseudomonas corneal ulcer in the rabbit.

Norfloxacin is a new synthetic antibiotic with a broad spectrum of activity against gram-positive and gram-negative bacteria, and is more effective than the aminoglycosides against P aeruginosa. In this study norfloxacin was particularly effective in treatment of P aeruginosa infection of the rabbit cornea, and caused no toxicity in normal rabbit eyes after prolonged administration. The addition of silver to norfloxacin enhances its antipseudomonal activity, and broadens its spectrum to include antifungal activity. In this study, silver norfloxacin appears to be the most effective antibiotic against P aeruginosa corneal ulcer in the rabbit. Because of its broad antibacterial spectrum, silver norfloxacin may be useful in the initial treatment of bacterial corneal ulcer before the identity of the bacteria is known. Because of its low toxicity in topical administration, and its antifungal and antibacterial activity, silver norfloxacin may be helpful in prophylaxis against infection in chronic corneal ulcers.

Topical therapy and the development of silver sulfadiazine.

Topical therapy is a selective approach to the prevention and treatment of infection in burns and other surgical wounds. Effective compounds possess certain chemical and physical properties. Prerequisites include low solubility, slow absorption, nonreactivity with wound exudates, proteins and ions and ability to achieve prolonged antimicrobial activity in the wound. These compounds yield much higher levels in the zone of infection than can be achieved by diffusion into the wound after systemic administration. The wide spectrum of antibacterial activity, the low toxicity, minimal tissue reaction, ease of application suggest that topical silver sulfadiazine therapy can safely be extended to other wound infections, wound covers and certain transplant materials.

Sulfadiazine silver-resistant Pseudomonas in Burns. New topical agents.

Sulfadiazine silver-resistant strains of Pseudomonas aeruginosa isolated from burned patients from several countries are sensitive to sulfadiazine silver in vitro, but in burned mice and rats resist topical therapy with sulfadiazine silver. In searching for an effective topical agent against these resistant organisms, we found that FPQC (1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7[1-piperazinyl]-quinoline-carboxylic acid) and its silver salt are effective both in vitro and in vivo. In vitro, their minimal inhibitory concentrations are ten to 20 times lower than that of sulfadiazine silver. In burned mice infected with resistant Pseudomonas strains, mortality in groups receiving topical therapy with FPQC or FPQC silver is 0%, but 80% to 100% with sulfadiazine silver and 100% without treatment. Similar results were obtained in burned rats. The efficacy of FPQC and FPQC silver in vivo may represent discovery of new agents of known low toxicity that are useful in topical burn therapy.