Effects of the level of asphyxia during delivery on viability at birth and early postnatal vitality of newborn pigs

Newborn pigs (n = 117) were used to provide information on the relationships of degree of asphyxia during delivery, viability at birth, and some striking aspects of postnatal vitality including survival, interval between birth and first udder contact and between birth and first suckling, rectal temperature at 24 h of life (RT24), and growth rate over the first 10 d of life. The degree of asphyxia at birth was estimated from cord blood pCO2, pH, and lactate levels. Onset of respiration, heart rate, skin color, and attempts to stand during the first minute after birth were used to estimate the viability score. Neonatal asphyxia, i.e., decreased blood pH and increased blood pCO2 and lactate, was associated with the production of unusually high levels of catecholamines. The degree of asphyxia increased with late position in the birth order (P < .01) and was higher in piglets born posteriorly (P < 0.5). Further, the average blood pCO2 within a litter increased (P < .05) with litter size. The was an inverse relationship between the degree of asphyxia and the viability score (P < .001). Highly viable piglets reached the udder more rapidly (P < .001) and had a higher RT24 (P < .001) than those of low viability. Plasma glucose concentrations increased with blood pCO2 and plasma epinephrine concentrations (P < .001). Neonatal asphyxia reduced postnatal vitality by delaying the first contact with the udder (P < .03) and was associated with a lower RT24 (P < .05), growth rate (P < .001), and survival over 10 d (P < 0.06). These variables, i.e., interval between birth and first udder contact, RT24, and growth rate, were correlated with birth weight (P < .001); RT24 was also shown to decrease (P < .001) with the time taken to reach the udder. Overall, results suggest that piglet suffering from asphyxia during delivery are less viable at birth and less prone to adapt to extrauterine life.     

Protective effect of povidone-iodine ointment against skin lesions induced by sulphur and nitrogen mustards and by non-mustard vesicants

The concentration of thyreoglobulin (tg) was determined for death caused by hanging, strangulation by ligature, and throttling. Cases of sudden death (traumatic aortic rupture, penetrating wounds of the heart) were used for comparison. The mean values in cases of hanging (149.9 +/- 202.3 ng/ml), strangulation by ligature (193.1 +/- 173.3), manual strangulation (561.6 +/- 173.9) are distinguishable from violent acute deaths (23.3 +/- 27.6) and living healthy individuals (17.3 +/- 16.1). By means of statistical comparisons, significant differences were found between throttling and strangulation by ligature and between throttling and hanging (adjusted P < 0.001). In connection with examination of the bodies high tg values can be regarded as a vital reaction in obstructive asphyxia.     

The diagnostic significance of coagulated heart blood in cases of death by acute asphyxia (author's transl)

In cases of death by asphyxia, such as strangulation, hanging, drowning, lack of oxygen, compression of the chest, and carbon monoxide poisoning, the frequency of the liquid and coagulated state of blood in the heart was examined. Coagulated blood in the right heart can be found in cases of strangulation, hanging, and drowning, if simultaneously an elevated blood alcohol was present. The diagnostic significance of this result is discussed.     

Multiple epidural metastases and development of secondary metastatic spinal cord compression]

The purpose was to examine the frequency of initial multiple epidural metastases, and the occurrence of secondary spinal cord compression (SCC). One hundred and seven patients with SCC from a histologically verified solid tumour were followed prospectively with regular neurological examinations until death. Multiple metastases were demonstrated in 37 (35%). Eight (7.5%) patients developed a second occurrence of SCC all in a new location within the spinal canal. The second occurrence of SCC was found with the same frequency in patients with single metastases (7.1%) compared to patients with multiple metastases (8.1%). The median survival time after the diagnosis of spinal cord compression was 3.4 months, while in the group of patients who developed a second occurrence of SCC the median survival time was 9.2 months. We concluded that only symptomatic epidural metastases should be irradiated, and that all patients treated for SCC should be followed regularly and observed for development of a second SCC.     

A reproducible model of circulatory arrest and remote resuscitation in rats for NMR investigation

BACKGROUND AND PURPOSE: Because noninvasive physiological monitoring of cerebral blood flow, metabolic integrity, and brain ion and water homeostasis can now be accomplished with new, state-of-the-art MR spectroscopy and imaging techniques, it is appropriate to develop controllable and reproducible animal models that permit prolonged circulatory arrest and resuscitation in the magnet and also allow for studies of long-term survival and outcome. We have developed such a model in rats that involves minimal surgical preparations and can achieve resuscitation remotely within precisely controlled time. METHODS: Cardiac arrest was induced by asphyxiation, the duration of which ranged from 8 to 24 minutes. Resuscitation was achieved remotely by a slow, intra-aortic infusion of oxygenated blood (withdrawn either from the same rat before asphyxia or from a healthy donor rat) along with a resuscitation cocktail containing heparin (50 U/100 g), sodium bicarbonate (0.1 mEq/100 g), and epinephrine (4 micrograms/100 g). The body temperature was measured by a tympanic thermocouple probe and was controlled either by a heating pad (constant tympanic temperature = 37 degrees C) or by warm ambient air (constant air temperature = 37 degrees C). Interleaved 31P/1H nuclear magnetic resonance (NMR) spectroscopy was used in a selected group of rats to measure the cerebral metabolism before and during approximately 20 minutes of circulatory arrest and after resuscitation. RESULTS: The overall success rate of resuscitation, irrespective of the duration of cardiac arrest, was 82% (51 of 62). With a programmed infusion pump, the success rate was even higher (95%). The survival time for rats subjected to 15 and 19 minutes of asphyxia with core temperature tightly controlled was significantly lower than that with ambient temperature control (P < 0.001 and P < 0.04, respectively). High-quality NMR spectra can be obtained continuously without interference from the resuscitation effort. Final histological examinations taken 5 days after resuscitation showed typical neuronal damages, similar to those found in other global ischemia models. CONCLUSIONS: Because the no-flow time and resuscitation time can be precisely controlled, this outcome model is ideally suited for studies of ischemic and reperfusion injuries in the brain and possibly in other critical organs, permitting continuous assessment of long-term recovery and follow-up in the same animals.     

Brain death: neuropathological findings and forensic implications

'Brain death' is defined pathophysiologically as intracranial circulatory arrest. The morphological features of brain death include cerebral edema, absence of reactive changes, and--after an interval of 15-36 h--the morphological hallmarks of respirator brain: edema, global softening of the brain, dusky discoloration of the gray matter, and often necrotic and sloughing tonsillar herniations. The following implications of brain death for forensic medicine are discussed: discriminating between respirator and autolytic brain, declaration of death, determining the time of brain death versus the time of the traumatic event leading to brain death, and neuropathological control of the clinical diagnosis of brain death. These issues are elucidated and their bearing on forensic practice is illustrated by several real-life situations. Thus, neuropathological examination in the case of clinically diagnosed brain death is--without doubt--necessary in order to answer several questions often or regularly expected.     

Concentrated professional education to implement routine referral legislation increases organ donation

Penetrating injuries to the abdominal aorta most often result in rapid exsanguination and death. Immediate surgical intervention may result in control of hemorrhage and survival of the patient. Rarely, hemorrhage after aortic injury may be contained by surrounding tissues, resulting in pseudoaneurysm formation. Traumatic pseudoaneurysms may rupture at any time, and this is usually a fatal event. A 47-year-old man recently presented with a supraceliac abdominal aortic pseudoaneurysm that ruptured into the right chest 28 years after a gunshot wound to the back. This report describes the pathophysiology, diagnosis, and treatment of traumatic pseudoaneurysms of the abdominal aorta and includes a review of the literature. This is a case in which a traumatic pseudoaneurysm of the abdominal aorta was successfully repaired by surgery after rupture into the thorax and is the first such case to be reported in the literature.     

Influence of chronic administration of L-DOPA on event-related desynchronization of mu rhythm preceding voluntary movement in Parkinson''s disease

Casein zymographic assays were performed to identify changes in mu-calpain and m-calpain activity in naive, sham-injured, and injured rat cortex at 15 minutes, 3 hours, 6 hours, and 24 hours after unilateral cortical impact brain injury. Cortical samples ipsilateral and contralateral to the site of injury were separated into cytosolic and total membrane fractions. Marked increases in mu-calpain activity in cytosolic fractions in the ipsilateral cortex occurred as early as 15 minutes, became maximal at 6 hours, and decreased at 24 hours to levels observed at 15 minutes after injury. A similar temporal profile of cytosolic mu-calpain activity in the contralateral cortex was observed, although the increases in the contralateral cortex were substantially lower than those in the ipsilateral cortex. Differences were also noted between cytosolic and total membrane fractions. The detection of a shift in mu-calpain activity to the total membrane fraction first occurred at 3 hours after traumatic brain injury and became maximal at 24 hours after traumatic brain injury. This shift in mu-calpain activity between the two fractions could be due to the redistribution of mu-calpain from the cytosol to the membrane. m-Calpain activity was detected only in cytosolic fractions. m-Calpain activity in cytosolic fractions did not differ significantly between ipsilateral and contralateral cortices, and increased in both cortices from 15 minutes to 6 hours after injury. Relative magnitudes of m-calpain versus mu-calpain activity in cytosolic fractions differed at different time points after injury. These studies suggest that traumatic brain injury can activate both calpain isoforms and that calpain activity is not restricted to sites of focal contusion and cell death at the site of impact injury but may represent a more global response to injury.     

Spinal cord compression in metastatic cervical cancer

Spinal cord compression secondary to metastatic cervical cancer may not be considered as a possible cause of neurologic symptoms by primary care physicians who do not often treat these patients. Delays in diagnosis and treatment may result in irreversible but potentially preventable neurologic changes. This report describes 5 cases of spinal cord compression in patients with metastatic cervical carcinoma, 2 of whom were previously undiagnosed with cervical cancer. These 2 patients represent 1.6% (2 of 121) of all new cervical cancer cases diagnosed during this time period. Two of 5 patients (40%) with spinal cord compression showed improvement following therapy by regaining the ability to walk, while none of the remaining patients had further acute deterioration of neurologic function. The mean survival of patients presenting with spinal cord compression from cervical cancer in this series was 4 months (maximum 6 months). This series illustrates the relative frequency with which spinal cord compression is seen in patients with a new diagnosis of invasive cancer. This diagnosis should be considered when evaluating neurologic complaints in known cervical cancer patients or any woman with apparent pelvic pathology. Rapid diagnosis and treatment of these lesions, while not likely to improve overall survival significantly, can improve function and alleviate symptoms.     

Mesenteric vascular problems. A 26-year experience

Mesenteric vascular problems are infrequent, but may be catastrophic. During a 26-year period, 55 private patients were treated for the following disorders: (1) 12 patients with visceral artery aneurysms, (2) 8 with celiac compression syndrome, (3) 13 with chronic mesenteric ischemia, (4) 12 with acute mesenteric ischemia, and (5) 10 with mesenteric ischemia associated with aortic reconstructions. Splenic artery aneurysms were managed by excision and splenectomy, while celiac and hepatic had excision with graft replacement. Patients with celiac compression syndrome underwent lysis of the celiac artery. Two patients had compression of both celiac and superior mesenteric artery (SMA). One patient required vascular reconstruction of both arteries for residual stenoses. Patients having chronic mesenteric ischemia were treated with bypass grafts, with one death (7.7% mortality) and good long-term results. Those with acute mesenteric ischemia were treated by SMA embolectomy, bowel resection, or both, with a mortality of 67%. When associated with aortic reconstructions, mesenteric ischemia carried a mortality of 100% if bowel infarction occurred after operation, but when prophylactic mesenteric revascularization was performed at the time of aortic surgery, prognosis was greatly improved, with only one death among six patients. An aggressive approach including prompt arteriography with early diagnosis and surgical therapy is advocated for these catastrophic acute mesenteric problems.     

What do measures of flux tell us about vascular wall biology?

Fibronectin plays an important role in tissue repair and wound healing. Previous literature reports indicated that fibronectin could be a marker of vitality for wounds with a survival time of more than a few minutes. In order to verify these findings were performed immunohistochemical investigations on the expression of fibronectin in incised wounds of porcine skin inflicted into various anatomical regions in the early postmortem interval (0-5 min after circulatory arrest). Tissue specimens were collected 12-14 h postmortem and investigated for fibronectin on paraffin sections (alkaline phosphatase and monoclonal anti-alkaline phosphatase procedure). A markedly positive expression of fibronectin (not only next to the wound margin and clearly stronger than in normal undamaged skin) could be demonstrated in eleven out of 36 samples. A moderately positive fibronectin reaction was detectable in seven further specimens. Muscular contraction bands were observed in nine out of 36 specimens. The various reaction patterns of fibronectin cannot be finally explained, but are probably due to a passive transudation of skin tissue by blood components from injured vessels. As a result of these investigations the specificity and validity of fibronectin as a parameter of vitality has to be questioned. Fibronectin immunohistochemistry again reveals that the validity of parameters as vital criteria decreases when their manifestation time is short; postmortem/supravital induction seems to be possible resembling vital reactions in these cases.     

Neuroblastoma: a review of 21 cases presenting with spinal cord compression

The records of 21 children with neuroblastoma presenting with spinal cord compression, encountered over 17 years, were reviewed. Thirteen patients (61%) survive, free of neuroblastoma, at intervals ranging from nine months to 192 months (median, 78 months) from the time of diagnosis. The explanation for this relatively high survival rate was sought in an analysis of the cases which took into account age, site, extent of disease, and histology. The most significant features to emerge were the unusually high proportion of children under 12 months of age at presentation (11 of 21) most of whom survive (9 of 11) and the low incidence (3 of 21) of detectable at the time of diagnosis. The absence of a paraspinal mass was an unfavourable prognostic features (1 of 6 survives) whilst if a paraspinal mass was present, its anatomical level did not influence survival. In particular, children with retroperitoneal tumors fared no worse (survival, 6 of 7) than those with primary tumors at other sites (survival, 6 of 8). Morbidity was high (6 of 13), principally in infants with spinal cord compression from birth. Survival was also related to the histologic maturity of the tumor, even in the presence of metastases. Recommendations for management are made.     

Survival of asbestos insulation workers with mesothelioma

Malignant mesothelioma is a lethal disease. It is rare in the general population; however, workers exposed to asbestos suffer significant burdens of the neoplasm. The survival time of 457 consecutive fatal cases of pleural and peritoneal mesothelioma that occurred among 17,800 asbestos insulation workers observed prospectively from 1 January 1967 to 1 January 1987 was studied. Mean survival time from initial presentation of the disease to death was 11.4 months for the pleural mesothelioma patients compared with 7.4 months for the peritoneal group. This difference was statistically significant. Mean survival time from diagnosis to death was shorter for both groups of patients: 8.4 months for pleural mesothelioma v 5.8 months for the peritoneal cases. In conclusion, survival time in mesothelioma patients is short; most die within a year from the onset of the initial symptoms. No effective therapy is yet available.     

On reflection and prejudice

The condition referred to as "birth asphyxia" occurs as the result of a hypoxic-ischaemic insult during the process of labour and delivery. There is no standard clinical definition for birth asphyxia, but its incidence in term infants has been differently reported to be between 2.9 and 9.0 cases per 1000 deliveries. In term infants the risk of death appeared to be closely related to the duration that the Apgar score is severely depressed. The best predictor of disability in surviving infants is abnormal neurological behavior in the neonatal period referred to as hypoxic-ischaemic encephalopathy. Unfortunately, there are no generally accepted treatment regimens for birth asphyxia and traditional methods for treating hypoxic-ischaemic encephalopathy have not been shown to improve outcome.     

CT reconstruction of an unusual chronic posttraumatic aneurysm of the thoracic aorta

Chronic traumatic aneurysm of the thoracic aorta is an unusual occurrence. Previously, arteriography was performed on all patients seen in our institution with this entity to allow confirmation of the diagnosis and anatomic delineation for operation. A case of chronic traumatic aneurysm of the distal descending aorta discovered on a routine chest roentgenogram and evaluated with chest computed tomographic scanning with three-dimensional reconstruction is presented. It is our belief that not all thoracic aneurysms require arteriography, and improved methods of computed tomographic scanning allow adequate diagnosis and anatomic delineation with decreased morbidity and cost.     

Reperfusion injury as the mechanism of brain damage after perinatal asphyxia

Upon reperfusion of ischemic tissues, reactive oxygen metabolites are generated and are responsible for much of the organ damage. Experimental studies have revealed two main sources of these metabolites: 1) the oxidation of hypoxanthine to xanthine and on to uric acid by the oxidase form of xanthine oxidoreductase and 2) neutrophils accumulating in ischemic and reperfused tissue. Blocking either source will reduce reperfusion damage in a number of experimental situations. Although xanthine oxidoreductase activity may be unmeasurably low in organs other than liver and intestine, it may be involved in reperfusion injury elsewhere because of its localization in capillary endothelial cells. Time course considerations suggest that substrate accumulation and NADH inhibition of dehydrogenase activity may be more important in the pathogenesis than conversion of xanthine dehydrogenase into the oxidase form. Neutrophil accumulation may be partly due to oxidants in the first place, suggesting a link between the two sources of reactive oxygen metabolites. In the clinical context, many of the sequelae of perinatal asphyxia may be accounted for by reperfusion damage to organs such as brain, kidney, heart, liver, and lungs. During asphyxia, substrates of xanthine oxidase accumulate, upon resuscitation the cosubstrate oxygen is introduced, and evidence for oxidant production and effects has been obtained. In the pathogenesis of brain damage after asphyxia, both microvascular injury and parenchymal cell damage are important. Oxygen metabolites are involved in the former, but in the latter process their role is less clear because ischemia-reperfusion triggers not only oxidant production but many other phenomena, including gene activation, ATP depletion, glutamate accumulation, and increase of intracellular calcium. A severe insult results in cell necrosis, but more moderate asphyxia may cause delayed neuronal death through apoptosis. The time course of the changes in high energy phosphates as well as of selective neuronal death suggest that in the first hours of life there is a "therapeutic window," with future possibilities for prevention of permanent damage.     

ST segment elevation induced by class IC antiarrhythmic agents: underlying electrophysiologic mechanisms and insights into drug-induced proarrhythmia

Large-scale analyses of causes of neonatal deaths are usually based on death-certificate information. A new computer-based method has been introduced to define the cause of stillbirths and neonatal deaths in large amounts of material and to classify them according to two different models [Wigglesworth and Neonatal and Intrauterine death Classification according to (a)Etiology (NICE)]. The method is based on a combination of detailed information from health care registries and the death-certificate information. The present study aimed to compare these two classification models with a previously published method based solely on death certificate information [International Collaborative Effort (ICE)]. The study population comprised 2378 neonatal deaths in Sweden between 1987 and 1992. Cross-tabulation was made between the ICE classification and the other two classification models. In addition, case examples are presented in detail, exemplifying how classification errors arose. The ICE classification gives a rather low precision, notably for two important causes of death: asphyxia and immaturity. Among 328 infants dying from asphyxia according to computerized Wigglesworth classification, ICE classified 59% as asphyxia and 22% were labelled immaturity. When ICE classified the deaths as due to asphyxia, this was verified in only 50%. Among 792 infants dying from immaturity according to computerized Wigglesworth classification, 64% were classified as such by ICE. The findings cast doubts on the results of studies based exclusively on death-certificate information. Whenever possible in the analysis of neonatal deaths, death-certificate information should be supplemented with more detailed data. The computer-based method introduced here makes such analyses possible for large databases.     

Mortality and neurologic morbidity after repair of traumatic aortic disruption

BACKGROUND: Traumatic disruption of the thoracic aorta frequently results in death before operative repair. The determinants of mortality after repair, however, are uncertain. In addition, intraoperative strategies for reducing the incidence of spinal cord injury remain controversial. METHODS: The records of 45 consecutive patients undergoing repair of traumatic disruption of the thoracic aorta at a single institution during a 9-year period were reviewed in a retrospective fashion. Patient age ranged from 15 to 81 years (mean age, 33.9 years). Twenty-two patients (49%) had multiple associated injuries, and 8 (18%) had isolated aortic injuries. Nine patients (20%) experienced preoperative hypotension (systolic blood pressure of less than 90 mm Hg). Repair was performed with partial bypass in 22 patients, a heparinized shunt in 2, and no distal perfusion (clamp and sew technique) in 21. RESULTS: Nine patient (20%) died after operation. Multivariate logistic regression analysis of preoperative and intraoperative variables identified advancing age and preoperative hypotension as independent predictors of operative death. The presence of associated injuries was not an independent predictor of operative death. All 4 patients with injuries proximal to the aortic isthmus died. Ten patients were excluded from analysis of spinal cord injury either because of preoperative neurologic deficit or because of death before postoperative evaluation. Six (17%) of the remaining 35 patients had development of paraplegia: 5 of the 15 patients having the clamp and sew technique, 1 of the 2 with a shunt, and 0 of the 18 patients with bypass (p < 0.05, clamp and sew versus bypass). In the clamp and sew group, patients in whom paraplegia developed had significantly longer aortic clamp times than those without neurologic injury (40.6 +/- 4.4 minutes versus 28.7 +/- 2.9 minutes, respectively; p < 0.05). CONCLUSIONS: Advancing age, preoperative hypotension, and perhaps injury location are important determinants of death after repair of traumatic disruption of the thoracic aorta. Adjunctive perfusion with partial bypass should be used during repair to reduce the incidence of spinal cord injury.     

Factors associated with survival following secondary AIDS: 1988 to 1995

The second AIDS-defining condition diagnosed chronologically is referred to in this report as the secondary AIDS diagnosis. In this study, we examined survival following a secondary AIDS diagnosis using demographic and clinical factors known within 1 year before secondary AIDS diagnosis. In a prospective cohort of 2412 HIV-seropositive homosexual men observed in the Multicenter AIDS Cohort Study (MACS), 609 presented with a secondary AIDS diagnosis between January 1, 1988 and March 31, 1995. To analyze the data, we used survival analysis methods including the Kaplan-Meier product-limit estimator and extended Cox models that allow for nonproportional hazards. The median survival time after a secondary diagnosis was 10.3 months. Rapidity of progression from an initial AIDS diagnosis to a secondary diagnosis was not associated with survival. Drug treatment did not show a beneficial effect because of confounding by indication (i.e., selection bias) and limited efficacy on advanced disease of treatments available prior to 1995. However, a beneficial effect was captured by the use of calendar periods as a proxy measure for the relative exposure to drug treatments. Later calendar year of secondary diagnosis, secondary Kaposi's sarcoma, and higher CD4+ cell count were found to be significantly (p < .05) associated with longer survival time. However, secondary AIDS diagnosis was a significant factor only in the short term. Using secondary Pneumocystis carinii pneumonia as the reference diagnosis, the relative hazard of death 3 months after the time of secondary Kaposi's sarcoma diagnosis was 0.56 (95% confidence interval [CI] = 0.36-0.89) whereas the relative hazard after concurrently diagnosed multiple secondary illnesses was 2.06 (95% CI = 1.26-3.38). After approximately 1 year from the secondary diagnosis, the type of diagnosis was no longer significantly associated with survival.