Human cadavers

Bir et al." have analyzed the effect of blunt ballistic impact of a baton-type, less-lethal projectile on the thoracic region using human cadavers. She determined human-response corridors and developed biomechanical surrogates, which can be used for testing different new projectiles for their blunt ballistic impact. The human-response force corridor for blunt thoracic impact by a thermoplastic polyurethane-based baton round with 37 mm diameter, weighing 30 g, and traveling... 

Given the overwhelming influence of the physical properties of skin in determining bioavailabilities via the dermal route, assessment of dermal penetration is one area in metabolism and toxicology where in vitro methods can be effectively used to predict in vivo results and to screen chemicals. Apparatus and equipment exist that one can use to maintain sections of skin (obtained from euthanized animals or from human cadavers or surgical discard) for such experiments (Holland et al., 1984). These apparatus are set up to maintain the metabolic integrity of the skin sample between two reservoirs the one on the stratum comeum side, called the application reservoir and the one on the subcutaneous side, called the receptor reservoir. One simply places radiolabeled test material in the application reservoir and collects samples from the receptor fluid at various time points. 

R. C. Wester, J. Christoffel, T. Hartway, N. Poblete, H. I. Maibach, and J. Forsell. Human cadaver skin viability for in vitro percutaneous absorption Storage and detrimental effects of heat-separation and freezing. Pharm. Res. 15 82-84 (1998). 

Although ciclosporin and tacrolimus applied systemically improve psoriatic lesions, they are clearly less active when applied topically. Therefore, liposomal preparations have been developed. Indeed, ciclosporin penetrates deeper strata of rodent and human cadaver skin more efficiently when incorporated into liposomes [51], Moreover, tacrolimus concentrations in murine skin have increased ninefold, and skin graft survival prolonged, if the drug is liposome encapsulated [52]. This indicates that topical psoriasis therapy with tacrolimus may become possible. At present, topical tacrolimus is confined to the less recalcitrant forms of mild eczema. 

Somatotropin or growth hormone (GH) Human cadaver pituitaries Treatment of severe GH deficiency in children... 

Growth hormone is a 191-amino-acid peptide with two sulfhydryl bridges. Its structure closely resembles that of prolactin. In the past, medicinal GH was isolated from the pituitaries of human cadavers. However, this form of GH was found to be contaminated with prions that could cause Creutzfeldt-Jakob disease. For this reason, it is no longer used. Somatropin, the recombinant form of GH, has a 191-amino acid sequence that is identical with the predominant native form of human GH. 

Somatropin extracted from cadaveric human pituitaries was used to treat growth hormone-deficient patients until several cases of the fatal degenerative neurological disorder Creutzfeldt-Jakob disease were reported in the mid-1980s. Of 267 cases of iatrogenic Creutzfeldt-Jakob disease, 139 were caused by human cadaver-derived somatropin (SEDA-25, 479). 

The mammalian cell culture technique can be employed to produce clinically important biochemicals such as human growth hormones, interferon, plasminogen activator, viral vaccines, and monoclonal antibodies. Traditionally, these biochemicals had been produced using living animals or extracted from human cadavers. As examples, monoclonal antibodies can be produced by cultivating hybridoma cells in the peritoneal cavity of mice, and the human growth hormone to cure dwarfism can be extracted from human cadavers. However, the quantity obtained from these methods is quite limited for the wide clinical usages of the products. 

Roy, S. D. and E. Manoukian. 1994. Permeability of ketorolac acid and its ester analogs (prodrug) through human cadaver skinl. Pharm. Sci83 1548-1553. 

Initial proof of principle studies of ocular carotenoid RRS employed a laboratory-grade high-resolution Raman spectrometer and flat-mounted human cadaver retinas and eyecups. In Fig. 12.10, typical Raman spectra are shown for an excised eyecup, in which the excitation laser was aimed at the center of the macula, the fovea, and at two locations with increased eccentricities. In all cases, RRS spectra are obtained that display the... 

Transcutaneous Raman spectroscopic measurements using spatially offset optical fibers were reported less than a year later [59, 60]. The test systems were chicken tibiae and the humeri of human cadavers. The use of cadaveric and ex vivo specimens allowed validation of the measurements by comparison to exposed bone tissue. In these measurements a depth of 3-4 mm below the skin was reached. In vivo measurements began with a report of the Raman spectrum of a phalange of a human volunteer [61]. The periosteal surface was probably 1-2 mm below the skin and the mineral phosphate Vi was accurately reproduced, although incomplete separation of mineral and matrix spectra introduced errors in other bands. 

To give the particles the required momentum, they should be densely packed and rigid and have a well-defined narrow particle size distribution. Friable and oblique particles are not desirable because the penetration depth will increase if the particle characteristic is more variable (Hickey 2001). Studies have been performed with particles ranging from 20 to 40 J,m in size and 1.1 to 7.9 g/cm3 in density impacting human cadaver skin (Kendall et al. 2000). Velocities of up to 260 m/s were applied to particles of this size range. For many applications, smaller particles of about 1 to 4 j,m diameter may be required for an optimized delivery. To deliver particles of this size into the skin, higher densities and impact velocities are required. For this reason, gold particles are used as a carrier material for the delivery of plasmid DNA vaccines (Kendall et al. 2001). 

Before 1985, GH was obtained from human cadaver pituitary glands. A small number of individuals who received cadaver-derived pooled growth hormone preparations developed Creutzfeldt-Jakob disease, a fatal neurodegenerative disease that presented many years after GH treatment. (This... 

Figure 7.7. Agarose gel electrophoresis of total RNA. Total RNA from mouse skin (panel a, lane 2) and two human cadaver skin samples (panel b, lanes 1 and 2) were isolated by guanidine thiocyanate method and size fractionated on denaturing formaldehyde containing 1% agarose gel and stained with 0.5 pg/mL ethidium bromide. Note that in case of mouse skin RNA, two distinct ribosomal RNA bands (upper 28S and lower 18S bands) are clearly visible. In contrast, in case of human skin samples, which were collected several hours postmortem, there is partial RNA degradation as is evident by fuzzy 28S and 18S ribosomal RNA bands. RNA degradation is more pronounced in one of the samples than the other (panel b, compare lane 1 and lane 2). Ribosomal RNA bands are indicated by arrowheads. RNA size markers (Invitrogen, Carlsbad, CA) in the range 0.24 to 9.5 kb are in lane 1 (panel a) and lane 3 (panel b).

Advanced decay is associated with a significant increase in the concentration of soil nitrogen. The decomposition of a 68 kg human cadaver resulted in an increase in approximately 525 pg ammonium g 1 soil (Vass et al. 1992). Cadaveric material contains several other nutrients, such as P, potassium (K), calcium (Ca), and magnesium (Mg) (Table 2.1), which will enter the soil upon decomposition. Soil (3-5 cm) beneath a 68 kg human cadaver in advanced decay also contained 300 pg K g1 soil, 50 pg Ca g1 soil, and approximately 10 pg Mg g 1 soil (Vass et al. 1992). 

Rodriguez, W. C. and Bass, W. M. (1983). Insect activity and its relationship to decay rates of human cadavers in east Tennessee. J. Forensic Sci. 28,423-432. 

Vass, A. A., Bass W. M., Wolt, J. D. Foss, J. E., and Ammons, T. (1992). Time since death determination of human cadavers using soil solution. /. Forensic Sci. 37, 1236-1253. 

The majority of experimental studies in this field have used pig carcasses as models for human decomposition. However, one study has been reported that used human cadavers in an experimental capacity (Rodriguez and Bass 1985). The study conducted in Knoxville, Tennessee, involved the burial of six unembalmed human cadavers at varying depths and subsequent exhumation at varying intervals. Carrion insect activity was only observed on the bodies buried at a depth of approximately 30 cm (1 ft.). The insects were identified as larvae, pupae, and adults of the family Calliphoridae and Sarcophagidae. It was speculated that the adult flies laid their eggs in the small crevices in the soils above the remains and that the larvae then burrowed to the cadaver where further development ensued. The study was able to demonstrate that the depth at which the cadaver was buried directly affected access by carrion insects and subsequently the rate of decomposition. 

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