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Biomedical subjects

J D Gilbert

Publications and source records attributed to J D Gilbert.

At least 19 recordsLinked to original sources
PubMed2002

Epithelial cell mitotic arrest--a useful postmortem histologic marker in cases of possible colchicine toxicity.

Following ingestion of 30 mg of presumed benztropine (Cogentin) a 39-year-old male developed nausea, vomiting and diarrhea. His admission to hospital was soon followed by collapse and death. Histological examination, however, revealed increased numbers of mitotic figures in otherwise normal epithelial cells of the esophagus and bronchioles, a feature characteristic of colchicine toxicity. Subsequent toxicological analyses confirmed the presence of colchicine in the urine, but not in the blood. A dispensing error had resulted in substitution of colchicine for Cogentin. Histological findings had, therefore, provided evidence of colchicine toxicity and had guided subsequent toxicological evaluation. In suspected cases of colchicine toxicity, histological samples should, therefore, be taken from multiple sites along the gastrointestinal and respiratory tract in addition to other organs and tissues so that diagnostic morphological changes can be looked for.

Adult↗
PubMed2002

Fatal childhood vascular injuries associated with seat belt use.

The deaths of two children who were passengers in motor vehicles involved in accidents were directly attributable to vascular injuries derived from seat belts. In the first case, a 10-year-old boy died as a result of abdominal aortic transection by a lap seat belt, and in the second case a 15-year-old boy died as a result of transection of his common carotid artery by a lap-shoulder seat belt. Although these cases demonstrate rare fatalities associated with seat belt use, there is no doubt that seat belts have significantly reduced mortality and morbidity from traffic accidents. Although it is possible that a fatal outcome might have occurred in each of these cases from other injuries that might have been sustained had seat belts not been worn, appropriate positioning and size of seat belt harnesses might have avoided the lethal injuries.

Accidents, Traffic↗
PubMed2002

Childhood sporting deaths.

Exercise-induced collapse and sudden death are unusual in childhood. For this reason, a study was undertaken of a series of 12 cases of sudden death in childhood occurring during physical exertion associated with sporting activities. The age range was 7 to 16 years (mean 12.3 years, M:F ratio 5:1). Deaths resulted from trauma associated with the sporting activity, from an idiosyncratic response to exertion, or from exacerbation of a known underlying disease. Trauma was directly fatal (n = 4: vascular trauma in 1, head injury in 2, drowning in 1), exacerbated an underlying medical condition (n = 1: hypertrophic obstructive cardiomyopathy), or followed collapse from underlying organic disease (n = 1: drowning in epilepsy). Deaths after exertion occurred when there was an unexpected response to underlying occult disease (n = 4: aortic stenosis in 1, cerebral arteriovenous malformation in 1, hypertrophic obstructive cardiomyopathy in 1, coronary atherosclerosis in 1) or to preexisting known disease (n = 2: surgically corrected transposition of the great vessels in 1, asthma in 1). The fatal episodes often resulted from a complex interplay of a variety of factors, including physical exertion, possible trauma, and underlying organic disease. Testing of other family members may be indicated in cases where a rare, possibly familial, disease is found. Evaluation of cases required descriptions of activities before death, information from the medical history of the deceased, and detailed findings from the autopsy.

Adolescent↗
PubMed2001

Traditional punishment and unexpected death in Central Australia.

Three cases of traditional punishment in Central Australian Aboriginal men are presented in which the thighs were speared or stabbed as part of a "payback" system. In two cases, an unexpected effect of the stabbing or spearing was death due to severing of major leg vessels. The relationship between customary Aboriginal law and general law in Australia has not been clearly defined; however, these cases demonstrate that significant and untoward effects may result from traditional punishments. Pathologists working near traditional Australian Aboriginal communities may still encounter such injuries at autopsy.

Adult↗
PubMed2001

Characteristic features of suicidal drownings: a 20-year study.

A retrospective study of cases of drowning suicide was undertaken at the Forensic Science Centre in Adelaide, South Australia for the period April 1980 to March 2000. A total of 123 cases were found, with 76 males (age, 16-88 years; average, 50.5 years; standard deviation [SD], 20.1 years) and 47 females (age, 34-88 years; average, 60.6 years; SD, 13.9 years). There were 66 fresh water drownings and 57 saltwater drownings. Female victims were significantly older than male victims for both fresh water and saltwater drownings (P < .05 and P < .01, respectively). Deaths in young women were rare. No temporal trend in drowning suicides could be shown, with annual numbers varying from 0 to 12 cases (average, 6.15; median, 7). Women preferentially chose the ocean or bath to drown themselves in, whereas males chose rivers, ditches, and lakes. Swimming pools were rarely used for suicide in this population; alcohol use was not usual; and there was often a significant history of mental illness.

Adolescent↗
PubMed2001

Arrhythmogenic left ventricular dysplasia' and sudden death.

A 32-year-old man who died suddenly and unexpectedly was found at autopsy to have prominent fatty infiltration of his left ventricle with fibrous scarring, in the presence of normal coronary arteries. The right ventricle was minimally involved. A diagnosis of ventricular dysplasia largely limited to the left ventricle was made. Subsequent family screening identified a brother with clinical manifestations of ventricular dysplasia. This case provides further evidence for the association of left ventricular dysplasia with sudden death, and demonstrates that left ventricular involvement may also be inheritable. Whether predominantly left ventricular dysplasia is a manifestation of right ventricular dysplasia, or is a separate entity, is yet to be determined.

Adult↗
PubMed2001

Septo-optic dysplasia and unexpected adult death--an autopsy approach.

A 20-year-old woman who suffered from septo-optic dysplasia died unexpectedly following a presumed viral gastroenteritis. Autopsy and neuropathological examination confirmed optic nerve hypoplasia with absence of the septum pellucidum. Marked adrenal gland hypoplasia reflected hypothalamic hypopituitarism. The small and large intestines were dilated and filled with liquid fecal material. This case demonstrates that individuals with septo-optic dysplasia may be at risk of unexpected death at all ages. The complexity of mechanisms of death in rare dysmorphic conditions may be overlooked if relevant clinical information is not available at the time of autopsy and unless specific steps are taken to clearly delineate the underlying features of the condition.

Adrenal Gland Diseases↗
PubMed2001

Glycine toxicity and unexpected intra-operative death.

A rare complication of the use of glycine irrigation fluid during prostatic surgery in a 69-year-old man is described. Following cystolithopexy and transurethral resection of the prostate for benign prostatomegaly, abdominal distension developed with increasing ventilatory pressures. Despite retroperitoneal fluid evacuation at subsequent urgent laparotomy, cardiac arrest occurred that was not amenable to resuscitation. At autopsy a traumatic defect in the posterior bladder wall filled with calculus debris was confirmed that did not communicate with the peritoneal cavity. Hyponatremia with markedly elevated levels of blood, urine, and body fluid glycine were demonstrated. Death was, therefore, attributed to glycine toxicity following tracking of glycine through a surgical defect in the posterior bladder wall. Careful dissection of surgical sites is required in such cases to demonstrate any additional trauma that may be associated with the fatal episode. Analysis of body fluids for glycine and electrolytes is also necessary to assist in the determination of possible mechanisms of death.

Aged↗
PubMed2000

In vivo antitumor activity of ONYX-015 is influenced by p53 status and is augmented by radiotherapy.

The E1B-deleted, replication-competent ONYX-015 (dl1520) adenovirus was originally described as being able to selectively kill p53-deficient cells due to a requirement of p53 inactivation for efficient viral replication. This hypothesis has become controversial because subsequent in vitro studies have demonstrated that the host range specificity of ONYX-015 is independent of p53 gene status. Using a pair of isogenic cell lines that differ only in their p53 status, we demonstrate here that although ONYX-015 can replicate in both p53 wild-type and mutant cells in vitro, the virus demonstrates significantly greater antitumor activity against mutant p53 tumors in vivo. Moreover, ONYX-015 viral therapy can be combined with radiation to improve tumor control beyond that of either monotherapy. The results demonstrate that ONYX-015 can discern in vivo between tumors having a different p53 status and that it may be an effective neoadjuvant to radiation therapy.

Adenoviridae↗
PubMed2000

Double suicide gene therapy augments the antitumor activity of a replication-competent lytic adenovirus through enhanced cytotoxicity and radiosensitization.

Replication-competent adenoviruses may provide a highly efficient means of delivering therapeutic genes to tumors. Previously, we evaluated in vitro a replication-competent adenovirus (Ad5-CD/TKrep) containing a cytosine deaminase (CD)/herpes simplex type 1 thymidine kinase (HSV-1 TK) fusion gene that allows lytic viral therapy to be combined with double suicide gene therapy. Both the CD/5-FC and HSV-1 TK/GCV enzyme/prodrug systems enhanced the tumor cell-specific cytopathic effects of the Ad5-CD/TKrep virus in vitro and sensitized cells to radiation. To extend these in vitro findings in vivo, we evaluated the antitumor activity of the Ad5-CD/TKrep virus in combination with double prodrug therapy and radiation therapy. The Ad5-CD/TKrep virus independently demonstrated significant antitumor activity against C33A cervical carcinoma xenografts. Therapeutic outcome was dramatically improved with systemic administration of double, but not single, prodrug (5-FC + GCV) therapy. When used in a neoadjuvant setting, Ad5-CD/TKrep-mediated double suicide gene therapy dramatically potentiated the effectiveness of radiation therapy. The trimodal approach of Ad5-CD/TKrep viral, double suicide gene, and radiotherapies produced significant tumor regression and ultimately 100% tumor cure. The results demonstrate the high therapeutic potential of the trimodal approach and provide a solid foundation for future clinical trials.

Adenoviridae↗
PubMed2000

Evaluation of the biodistribution, persistence, toxicity, and potential of germ-line transmission of a replication-competent human adenovirus following intraprostatic administration in the mouse.

Adenovirus-mediated gene transfer may hold much promise in the treatment of human cancer. However, concerns regarding vector dissemination beyond the target tissue, particularly with replication-competent viruses, require an evaluation of the persistence of viral infection in collateral tissue and vector-associated toxicities. In addition, for indications such as prostate cancer, the proximity of the point of viral administration to organs of the male reproductive system raises concerns regarding inadvertent germ-line transmission of genes carried by the virus. To address these concerns, the biodistribution, persistence, toxicity, and potential of germ-line transmission of a replication-competent adenovirus (Ad5-CD/TKrep) following intraprostatic administration in the mouse was examined. Ad5-CD/TKrep (10(10) vp, 5 x 10(11) vp/kg) was injected intraprostatically on Day 1 of the study and its presence in the major organs of the male urogenital tract (prostate, testes, seminal vesicles, and urinary bladder) and liver was determined on Days 8 and 29. For comparison, a parallel group of animals was injected with the same dose of a related replication-defective Ad5-FGNR virus. To evaluate germ-line transmission, Ad5-CD/TKrep-injected males were mated to females on Days 8 and 29 and resulting embryos were examined for AdS-CD/TKrep viral DNA. Ad5-CD/TKrep viral DNA was detected in all major organs of the adult male urogenital tract and liver 7 and 28 Days postinjection. Interestingly, relative to the replication-defective Ad5-FGNR adenovirus, the replication-competent Ad5-CD/TKrep virus accumulated to a much greater level (approximately 300-fold) and persisted for a longer period of time in prostate, testes, and liver. This difference could not be explained on the basis of differences in viral infectivity, suggesting that the AdS-CD/TKrep virus may be capable of replicating in mouse tissues in vivo. In vitro infection of six mouse cell lines representing prostate, testes, and liver demonstrated that the Ad5-CD/TKrep virus was indeed capable of replicating in these mouse cell types, albeit with reduced efficiencies relative to human cells. Despite the fact that the Ad5-CD/TKrep vector persisted in the adult male gonads and may have replicated in vivo, we observed no evidence of germ-line transmission in 149 offspring examined. To evaluate the toxicity of combining Ad5-CD/TKrep viral therapy with CD/5-FC and HSV-1 TK/GCV suicide gene therapies as a prerequisite for a human trial, an escalating dose (10(8), 10(9), 10(10) vp) of Ad5-CD/TKrep was administered intraprostatically followed by 7 days of 5-FC and GCV double prodrug therapy. Although the virus persisted in the mouse urogenital tract and liver for up to 28 days postinjection, most of the toxicities observed were expected, minimal, and self-limiting. These results lead us to believe that intraprostatic administration of the Ad5-CD/TKrep virus to humans concomitant with double suicide gene therapy will be associated with acceptable toxicities and will not result in vertical transmission of viral-encoded genes through the germ line.

Adenoviridae↗
PubMed2000

Unexpected death in association with an occult posterior lingual abscess.

An 82 year old woman was found unexpectedly dead in bed on the day of admission to hospital for the investigation of difficulty breathing. During a barium swallow examination after admission she was thought to have aspirated contrast material. At autopsy a large posterior lingual abscess was found, with barium in the airways. Death was attributed to a combination of upper airway narrowing associated with the abscess, chronic lung disease and possible aspiration of barium. This case demonstrates an unusual sequence of events associated with localised upper airway sepsis. It also confirms the importance of careful examination of the upper aerodigestive tract at autopsy in individuals of all ages.

Journal Article↗
PubMed2000

Pathologic features of childhood pedestrian fatalities.

A retrospective analysis of 68 cases of fatal childhood pedestrian accidents in South Australia that occurred over a 20-year period from January 1977 to December 1996 was undertaken. The age range was 12 months to 16 years (average, 7.6 years), with a male to female ratio of 41:27. The most common site of significant injury was the head (91.2%), followed by the abdomen (50%), chest (47.1%), and neck (38.2%). The most frequently encountered significant injury combinations involved the head, chest, and abdomen (14.7%); the head and chest (11.8%); and the head, neck, and abdomen (11.8%). Injuries were severe, consisting of extensive compound and comminuted skull fractures, neck fractures, and massive intraparenchymal brain and internal organ damage with avulsions and fragmentation. Non-life-threatening limb injuries occurred in 88% of cases. A distinct subgroup involved infants and younger children playing in driveways at home who were hit by reversing vehicles. The injuries were often of such a severe nature that death was instantaneous and with no possibility of successful medical intervention. More deaths occurred during the winter than summer months.

Abdominal Injuries↗
PubMed2000

Pathologic features of fatal shark attacks.

To examine the pattern of injuries in cases of fatal shark attack in South Australian waters, the authors examined the files of their institution for all cases of shark attack in which full autopsies had been performed over the past 25 years, from 1974 to 1998. Of the seven deaths attributed to shark attack during this period, full autopsies were performed in only two cases. In the remaining five cases, bodies either had not been found or were incomplete. Case 1 was a 27-year-old male surfer who had been attacked by a shark. At autopsy, the main areas of injury involved the right thigh, which displayed characteristic teeth marks, extensive soft tissue damage, and incision of the femoral artery. There were also incised wounds of the right wrist. Bony injury was minimal, and no shark teeth were recovered. Case 2 was a 26-year-old male diver who had been attacked by a shark. At autopsy, the main areas of injury involved the left thigh and lower leg, which displayed characteristic teeth marks, extensive soft tissue damage, and incised wounds of the femoral artery and vein. There was also soft tissue trauma to the left wrist, with transection of the radial artery and vein. Bony injury was minimal, and no shark teeth were recovered. In both cases, death resulted from exsanguination following a similar pattern of soft tissue and vascular damage to a leg and arm. This type of injury is in keeping with predator attack from underneath or behind, with the most severe injuries involving one leg. Less severe injuries to the arms may have occurred during the ensuing struggle. Reconstruction of the damaged limb in case 2 by sewing together skin, soft tissue, and muscle bundles not only revealed that no soft tissue was missing but also gave a clearer picture of the pattern of teeth marks, direction of the attack, and species of predator.

Adult↗
PubMed2000

Methadone maintenance programs--a two-edged sword?

Retrospective review was undertaken of all autopsies in which methadone was detected at the Forensic Science Centre, South Australia, during a 3-year period from July 1996 to June 1999. Thirty-five cases were found in which methadone had either caused or contributed to death (age range = 14-54 years; average = 31 years; M:F = 3.4:1). Ten victims were participating in a methadone maintenance program, of whom four died within a week of enrollment. Eight victims (23%) not enrolled in a methadone maintenance program were found who had died after the use of "diverted" methadone (i.e., prescribed for someone else) (age range = 14-34 years; average = 25 years; M:F = 6:2). Deaths were directly attributable to methadone toxicity in seven of the eight cases, with additional drugs or alcohol being found in seven cases. Prevention of ongoing deaths caused by methadone diversion could be achieved by allowing only daily releases of methadone, with the addict having to consume the drug under close supervision.

Adolescent↗
PubMed2000

Predictors of torsades de pointes in rabbit ventricles perfused with sedating and nonsedating histamine H1-receptor antagonists.

Several nonsedating histamine H1-receptor antagonists are associated with torsades de pointes ventricular tachycardia. The objectives of this study were to: (i) compare electrocardiographic, monophasic action potential, and arrhythmogenic effects of sedating and nonsedating H1-receptor antagonists, and (ii) identify correlates of drug-induced torsades de pointes in an isolated ventricle model. Isolated, electrically paced (1-3 Hz) rabbit ventricles were Langendorff-perfused with either drug-free Tyrode's solution or one of the following: (i) the sedating H1-receptor antagonist hydroxyzine (0.1-30 microM), (ii) cetirizine, a nonsedating metabolite of hydroxyzine (1-300 microM), and (iii) the nonsedating, putatively arrhythmogenic H1-receptor antagonist astemizole (0.1-30 microM). Volume conducted electrocardiographic signals and monophasic action potentials from the periapical left ventricular endocardium and epicardium were recorded. There were no apparent changes in control (n = 15) or hydroxyzine-perfused (n = 7) hearts. Cetirizine (n = 13) produced a mild biphasic electrocardiographic QT interval prolongation and was associated with early afterdepolarizations, but not with torsades de pointes. Astemizole (n = 11) lengthened QT intervals, and at high concentration (30 microM) induced torsades de pointes in 10 of 11 hearts (P < 0.001 vs. all other groups). These findings are consistent with previously reported repolarizing current inhibition by cetirizine, but may additionally indicate "compensatory" inhibition of inward currents at higher concentrations. By contrast, astemizole-induced changes are consistent with unopposed repolarizing current inhibition.

Action Potentials↗