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Medical examiner asthma death autopsies: a distinct subgroup of asthma deaths with implications for public health preventive strategies.

OBJECTIVE: Asthma deaths have been increasing in the United States and worldwide. We studied medical examiner asthma death autopsy (MEADA) records for the state of Maryland, compared selected characteristics with state and national total asthma deaths (TADs), and comprehensively reviewed relevant literature to define characteristics of asthma deaths and to provide insight for the design of future preventive strategies directed at this subgroup. DESIGN: Protocols for autopsy and clinical data. SETTING: The Office of the Chief Medical Examiner of the State of Maryland. SUBJECTS: All MEADAs in the state of Maryland from 1988 through 1992. MAIN OUTCOME MEASURES: Descriptive analysis. RESULTS: Maryland MEADAs (63 cases) represented 16.62% of Maryland TADs (379 cases). Most common characteristics of individuals on whom autopsies were performed: inner-city residence; single; black male; 15 to 54 years old; history of asthma; no other significant medical condition; fatal episode more likely to begin at home; pronounced dead at hospital; time of death between midnight and 6 AM; no particular seasonality; and typical gross and/or microscopic pathology. Analysis also revealed that 17.46% of deceased asthma patients had a history of drug abuse; 12.69% had positive toxicology for drugs of abuse; 9.52% were infants and young children up to 4 years old, all of whom were found, unresponsive, at home; and white females comprised the highest number of TADs but the lowest number of MEADAs. CONCLUSION: Asthma education programs focused on asthmatic inner-city black males, especially those with a history of drug abuse, and on parents of inner-city asthmatic infants and children may be a useful preventive strategy. International, national, and regional MEADA databases may also be of use in the design and monitoring of preventive strategies directed at this subgroup.

Adolescent↗

The natural history of hepatitis C virus infection: host, viral, and environmental factors.

CONTEXT: Hepatitis C virus (HCV) infection may resolve (viral clearance), persist without complications, or cause end-stage liver disease (ESLD). The frequency and determinants of these outcomes are poorly understood. OBJECTIVE: To assess the incidence and determinants of viral clearance and ESLD among persons who acquired HCV infection from injection drug use. DESIGN AND SETTING: Community-based prospective cohort study with enrollment in 1988-1989 and a median follow-up of 8.8 years. SUBJECTS: A total of 1667 persons aged 17 years or older with a history of injection drug use and an HCV antibody-positive test result during follow-up. MAIN OUTCOME MEASURES: Viral clearance was assessed in a subset of 919 patients and defined as failure to detect HCV RNA in at least 2 consecutive samples collected 5 or more months apart. End-stage liver disease was assessed at semiannual visits and by review of medical records and death certificates and defined by the presence of ascites, esophageal varices, or hepatic encephalopathy, or when ESLD was stated as a cause of death. RESULTS: Viral clearance was observed in 90 persons who were compared with 722 with persistent viremia, while the viremia of 107 was not resolved. Viral clearance occurred more often in nonblacks (adjusted odds ratio [OR], 5.15; 95% confidence interval [CI], 2.60-10.17) and those not infected with human immunodeficiency virus (HIV) (adjusted OR, 2.19; 95% CI, 1.26-3.47). Forty cases of ESLD were observed throughout follow-up (incidence, 3.1 per 1000 person-years). In a multivariate model, risk of ESLD was higher for persons aged 38 years or older at enrollment (adjusted relative incidence, 3.67; 95% CI, 1.96-6.88) and who reported ingestion of more than 260 g of alcohol per week (adjusted relative incidence, 3.60; 95% CI, 1.73-7.52). Of 210 patients without ESLD randomly selected for biopsy, only 2 had cirrhosis. CONCLUSIONS: Our results indicate that although HCV infection can be self-limited or associated with ESLD, the majority of adults have persistent viremia without clinically demonstrable liver disease. Further research is needed to explain the less frequent clearance of HCV infection among black persons and to improve utilization of treatment for those infected in the context of injection drug use. JAMA. 2000;284:450-456

Adult↗

Apolipoprotein A, fibrinogen, age, and history of stroke are predictors of death in dialysed diabetic patients: a prospective study in 412 subjects.

BACKGROUND: Diabetic patients with end-stage renal failure (ESRD) have a high cardiovascular morbidity and mortality. The underlying mechanisms are not completely elucidated. The aim of our study was to define predictors of death in diabetic patients with end-stage renal disease. PATIENTS AND METHODS: We performed a prospective study in 35 dialysis centres in Germany between 1985 and 1994. To evaluate predictors and risk factors in this population we examined 412 diabetic patients at the time of admission to dialysis treatment (peritoneal dialysis (PD) or haemodialysis (HD)). Classification of the type of diabetes was done according the criteria of the National Diabetes Data Group [1,2]. Items assessed at the time of admission were coronary artery disease (CAD), peripheral occlusive disease (POD), and stroke. CAD was defined as a history of myocardial infarction with the corresponding changes in the ECG or luminal narrowing by more than 50% in at least one coronary artery upon coronarangiography; POD was defined as claudication and/or brachial-tibial ratio (BTR) less than 0.9 or a history of amputation. Assessment of the nutritional state comprised body mass index, skinfold thickness of the upper arm and lateral thorax area, and urea concentration. Cholesterol, HDL, LDL, apolipoprotein A (ApoA-I) and B (ApoB), triglycerides, lipoprotein(a) (Lp(a)), and fibrinogen were measured. As an index of disturbed cardiac innervation beat-to-beat variation was measured. Outcome measurements were causes of death (i.e. cardiac and non-cardiac) and time of survival. RESULTS: One hundred and eighty of 412 (44%) patients died during the observation period. Patients who died were older (61 +/- 12 versus 53 +/- 15 years P < 0.0001), had lower skin fold thickness (13.1 +/- 6.0 versus 15.1 +/- 7.3 mm P < 0.04), lower ApoA-I (100 +/- 35 versus 111 +/- 32 mg/dl P < 0.005) and higher fibrinogen (515 +/- 146 versus 451 +/- 155 mg/dl P < 0.02). Type II diabetic patients had a lower mean survival time than type I (34 versus 66 months P < 0.0006). The mode of renal replacement therapy (PD or HD) had no adverse effect on survival time. Survivors less frequently had a history of CAD, POD and stroke than non-survivors. In multivariate analysis ApoA-I, fibrinogen, age and stroke were independent predictors of cardiac and non-cardiac death in diabetic patients with end-stage renal failure. Lipid values and nutritional state did not independently predict the overall and cardiovascular mortality. CONCLUSION: This study in dialysed diabetic patients identifies several predictors of death, some of which are susceptible to intervention.

Adult↗

Natural death.

BACKGROUND: The increasing age of every human being is the beginning of the end of life, an obviously natural process, but any attempt to define the term 'natural death' soon encounters difficulties in defining what is meant by 'natural'. In the industrialized countries of the West, for example 'natural death' is thought of as the opposite of non-natural types of death such as accidental death, suicide, and homicide. OBJECTIVE: The aim of our present survey is to discuss the meaning of the term 'natural death' under a clinical, a forensic and a scientific point of view with regard to recent developments especially in molecular biology. CONCLUSION: If there are 'external' physical influences, a medical-technical manipulation, a therapeutic or molecular biological intervention cannot be definitely ruled out as the cause of death, then use of the term 'natural death' in general is open to question. It will only remain meaningful if it can be applied with a specific meaning in definite practical situations. Current research and medical technology, however, do not allow use of the term 'natural death' in its conventional sense: it can thus be stricken from the medical vocabulary.

Aging↗

Predictive role of the three-month CD4 cell count in the long-term clinical outcome of the first HAART regimen.

The aim was to evaluate whether the three-month CD4 cell counts are a reliable predictor of the long-term clinical outcome of HAART-treated patients, by an observational study of 585 patients initiating HAART in a clinical setting. Clinical failure was defined as the occurrence of new or recurrent AIDS-defining events or death, and was analysed by means of intention-to-treat, univariate and multivariate analyses. An adjusted Cox regression model was used to evaluate the effect of three-month CD4+ counts on clinical outcome. Clinical failure occurred in 65 patients (11.1%) during a median follow-up of 31 months (1-65) as a result of new AIDS-defining events (ADEs) in 48 patients, ADE recurrence in six, and death in 11. The mean (median; range) CD4+ counts were 156/microL (155; 4--529) in patients with and 362/microL (326; 18--1162) in patients without clinical failure (P < .0001). Moreover, the proportion of patients with mean CD4+ counts < 200 microL was higher in those experiencing subsequent clinical failure (chi2: 41.11; P< .00001). Multivariate analysis showed that baseline CD4+ counts < 50 microL, HIV-RNA > 100,000 copies/mL and AIDS at baseline predicted failure; after adjusting for three-month CD4+ counts, this marker was the only one independently associated with clinical failure (HR 2.93; 95% Cl: 1.16--7.38). The three-month immunologic response is a reliable predictor of long-term clinical outcome.

Acquired Immunodeficiency Syndrome↗

[Criteria of brain death. Spinal reflexes in 45 personal studies].

In 45 patients without spontaneous breathing or cranial reflexes, and in whom blood pressure had to be supported, spinal reflexes were obtained in 60% and polysynaptic spinal reflexes in 33%. In all cases angiography showed cerebral circulatory arrest and/or repeated EEG recording gave an isoelectric line. The presence of spinal reflexes, appearing most frequently 6-36 h after death (which we defined as a sudden fall in blood pressure below 80 mm Hg with absence of spontaneous breathing) is not in contradiction with the assumption of brain death. 9 patients without signs of intoxication showed, in addition, a fall in body temperature below 34 degrees C. Such a fall in body temperature also in agreement with the diagnosis of brain death.

Adolescent↗

Association between week of the month and death from acute myocardial infarction in Washington state, 1988 to 1997.

BACKGROUND: Deaths caused by substance abuse, circulatory disorders, and external causes such as suicide, homicide, and accidents are more likely to occur during the first week of the month than the last week of the preceding month. The purpose of this report is to determine if death caused by acute myocardial infarction occurs more often in the first 7 days of the month than in the last 7 days of the preceding month. METHODS AND RESULTS: This study used computerized death records for Washington state from 1988 to 1997. There were 401,314 deaths, of which 33,436 (8.3%) had an underlying cause of acute myocardial infarction. The week of the month during which death occurred was defined as occurring during the first 7 days of the month or the last 7 days of the preceding month. R, the ratio of the number of deaths during the first 7 days of the month to the number of deaths in the last 7 days of the preceding month multiplied by 100, was calculated, as were 95% confidence intervals. R values for other cardiac causes and substance abuse-related causes were also calculated. Deaths caused by acute myocardial infarction occurred more often in the first week of the month than in the last week of the previous month (R = 104.4, 95% confidence interval 101. 7-107.8). This pattern of death was most apparent for individuals > or =75 years of age (R = 107.3, 95% confidence interval 102.1-111.1) and was not evident for other cardiac causes, including congestive heart failure or myocardial ischemia. By comparison, substance abuse-related deaths occurred much more frequently during the first week of the month (R = 117.6, 95% confidence interval 110.0-125.8). CONCLUSIONS: This pattern of death for acute myocardial infarction may be in part caused by stressful events associated with the first week of the month.

Adult↗

Double blind dose-response study of zidovudine in AIDS and advanced HIV infection. Nordic Medical Research Councils' HIV Therapy Group.

OBJECTIVE: To compare the efficacy and side effects of 400 mg, 800 mg, and 1200 mg zidovudine daily in patients with AIDS or advanced HIV infection. DESIGN: Randomised, double blind, parallel group multicentre study. SETTING: Hospital departments of infectious diseases and dermatology in Denmark, Sweden, Norway, Finland, and Iceland. SUBJECTS: 474 patients: 126 (27%) with AIDS; 248 (52%) with HIV related symptoms; 100 (21%) with low CD4+ cell counts. INTERVENTIONS: Zidovudine 400 mg (160 patients), 800 mg (158), or 1200 mg (156) daily. All patients received one capsule from each of three bottles four times daily. MAIN OUTCOME MEASURES: Survival; incidence of new HIV related events; CD4+ cell count; quality of life; incidence of haematological side effects. RESULTS: 460 (97%) of the 474 patients had not received zidovudine previously. The median follow up period was 19 months, during which the death rates in the three treatment groups were 23% (36/160 patients), 23% (36/158), and 19% (30/156) respectively (p = 0.49; log rank test). One year after the trial was terminated the death rates were 38% (61/160), 41% (64/158), and 44% (68/156) respectively (p = 0.54). There was no significant difference between the groups in time to a new AIDS defining event or death, average number of events per patient, decline in CD4+ cell counts, wellbeing (visual analogue scale), or Karnofsky score. Zidovudine was withdrawn in 132 (28%) patients, mainly because of side effects (71 cases; 15%). The incidences of anaemia and leucopenia, time to first dose reduction, and numbers of patients withdrawn were all dose related. CONCLUSION: Zidovudine should be limited to 400-600 mg daily in patients with AIDS or advanced HIV infection.

Acquired Immunodeficiency Syndrome↗

The mouse anterior chamber angle and trabecular meshwork develop without cell death.

BACKGROUND: The iridocorneal angle forms in the mammalian eye from undifferentiated mesenchyme between the root of the iris and cornea. A major component is the trabecular meshwork, consisting of extracellular matrix organized into a network of beams, covered in trabecular endothelial cells. Between the beams, channels lead to Schlemm's canal for the drainage of aqueous humor from the eye into the blood stream. Abnormal development of the iridocorneal angle that interferes with ocular fluid drainage can lead to glaucoma in humans. Little is known about the precise mechanisms underlying angle development. There are two main hypotheses. The first proposes that morphogenesis involves mainly cell differentiation, matrix deposition and assembly of the originally continuous mesenchymal mass into beams, channels and Schlemm's canal. The second, based primarily on rat studies, proposes that cell death and macrophages play an important role in forming channels and beams. Mice provide a potentially useful model to understand the origin and development of angle structures and how defective development leads to glaucoma. Few studies have assessed the normal structure and development of the mouse angle. We used light and electron microscopy and a cell death assay to define the sequence of events underlying formation of the angle structures in mice. RESULTS: The mouse angle structures and developmental sequence are similar to those in humans. Cell death was not detectable during the period of trabecular channel and beam formation. CONCLUSIONS: These results support morphogenic mechanisms involving organization of cellular and extracellular matrix components without cell death or atrophy.

Animals↗

Changing incidence of AIDS-defining illnesses in the era of antiretroviral combination therapy.

OBJECTIVE: To determine the incidence of AIDS-defining opportunistic infections and malignancies over a 5-year period from 1992 to 1996. STUDY POPULATION: Subcohort of 1003 homosexual men with HIV infection and CD4 count less than 200 x 10(6) cells/l from the Frankfurt AIDS Cohort Study. METHODS: Data including the earliest date that a CD4 T-lymphocyte count < 200 x 10(6)/l was reached and the dates of AIDS-defining events were compiled from medical records. Incidence analyses for AIDS-defining events and death during the subsequent 5 years (1992-1996) were performed using rates per 100 person-years of exposure. RESULTS: During the observation period, the number of patients per year with CD4 T-lymphocyte counts < 200 x 10(6)/l varied between 402 and 511. In 1992, 56.7% of patients experienced at least one AIDS-defining illness, and 20.7% in 1996. The annual number of AIDS-defining events per 100 patient-years of observation declined from 143.5 in 1992 to 38.3 in 1996, and the number of AIDS-related deaths fell from 25.7 to 12.9. Analysis of the number of events confirmed this trend for malignancies and single opportunistic infections, with the exception of mycobacterial diseases. CONCLUSIONS: The incidence of AIDS-defining events in patients with advanced HIV infection at Frankfurt University Hospital has declined by more than 70% from 1992 to 1996.

AIDS-Related Opportunistic Infections↗

Advice to reduce dietary salt for prevention of cardiovascular disease.

BACKGROUND: Restricting sodium intake in elevated blood pressure over short periods of time reduces blood pressure. Long term effects (on mortality, morbidity or blood pressure) of advice to reduce salt in patients with elevated or normal blood pressure are unclear. OBJECTIVES: To assess in adults the long term effects (mortality, cardiovascular events, blood pressure, quality of life, weight, urinary sodium excretion, other nutrients and use of anti-hypertensive medications) of advice to restrict dietary sodium using all relevant randomised controlled trials. SEARCH STRATEGY: The Cochrane Library, MEDLINE, EMBASE, bibliographies of included studies and related systematic reviews were searched for unconfounded randomised trials in healthy adults aiming to reduce sodium intake over at least 6 months. Attempts were made to trace unpublished or missed studies and authors of all included trials were contacted. There were no language restrictions. SELECTION CRITERIA: Inclusion decisions were independently duplicated and based on the following criteria: 1) randomisation was adequate; 2) there was a usual or control diet group; 3) the intervention aimed to reduce sodium intake; 4) the intervention was not multifactorial; 5) the participants were not children, acutely ill, pregnant or institutionalised; 6) follow-up was at least 26 weeks; 7) data on any of the outcomes of interest were available. DATA COLLECTION AND ANALYSIS: Decisions on validity and data extraction were made independently by two reviewers, disagreements were resolved by discussion or if necessary by a third reviewer. Random effects meta-analysis, sub-grouping, sensitivity analysis and meta-regression were performed. MAIN RESULTS: Three trials in normotensives (n=2326), five in untreated hypertensives (n=387) and three in treated hypertensives (n=801) were included, with follow up from six months to seven years. The large, high quality (and therefore most informative) studies used intensive behavioural interventions. Deaths and cardiovascular events were inconsistently defined and reported; only 17 deaths equally distributed between intervention and control groups occurred. Systolic and diastolic blood pressures were reduced at 13 to 60 months in those given low sodium advice as compared with controls (systolic by 1.1 mm Hg, 95% CI 1.8 to 0.4, diastolic by 0.6 mm hg, 95% CI 1.5 to -0.3), as was urinary 24 hour sodium excretion (by 35.5 mmol/ 24 hours, 95% CI 47.2 to 23.9). Degree of reduction in sodium intake and change in blood pressure were not related. People on anti-hypertensive medications were able to stop their medication more often on a reduced sodium diet as compared with controls, while maintaining similar blood pressure control. REVIEWER'S CONCLUSIONS: Intensive interventions, unsuited to primary care or population prevention programmes, provide only minimal reductions in blood pressure during long-term trials. Further evaluations to assess effects on morbidity and mortality outcomes are needed for populations as a whole and for patients with elevated blood pressure. Evidence from a large and small trial showed that a low sodium diet helps in maintenance of lower blood pressure following withdrawal of antihypertensives. If this is confirmed, with no increase in cardiovascular events, then targeting of comprehensive dietary and behavioural programmes in patients with elevated blood pressure requiring drug treatment would be justified.

Antihypertensive Agents↗

Risk of suicide attempts after benzodiazepine and/or antidepressant use.

PURPOSE: Recent publications imply the existence of associations between psychotropic drugs use and risk of suicide. Some studies have measured the tissue level of these drugs in suicide deaths, while others compared toxicity indices, defined as number of suicide deaths per million prescriptions for individual antidepressants. Few of these studies used unexposed controls. The objective of this cohort study was to evaluate suicide attempts in subjects recently exposed to benzodiazepines and/or antidepressants, as compared to unexposed controls. METHODS: A population of 225,796 persons with prescriptions for benzodiazepines were selected from the Saskatchewan Health Data Bases. Controls consisted of 97,862 individuals who did not receive benzodiazepines. RESULTS: Stratifying the populations into antidepressant users and non-antidepressant users indicated that nonantidepressant users had statistically significant associations between suicide attempts and benzodiazepine use (odds ratio (OR) = 6.2), antipsychotic use, (OR = 2.6), and a history of past treatment for drug/alcohol abuse (OR = 13.4). Antidepressant users showed a statistically significant relation only with past treatment for drug/alcohol use (OR = 5.8). It is argued that the large OR for antidepressant use is due to confounding by indication. If so, the concept of toxicity index is misleading and should not be used. CONCLUSIONS: The association between benzodiazepine use and attempted suicide is especially high for nonantidepressant users, for the young, and for males. Whether this relationship is causal or not, physicians should be aware of the high potential for suicide attempts when prescribing benzodiazepines for patients in these high risk groups.

Adult↗

The effect of terminations of pregnancy for fetal abnormalities on trends in mortality to one year of age in Western Australia.

Summary highlighted the contribution of birth defects. Over this time there has also been an increasing number of terminations of pregnancy for fetal abnormality. However, the effect of these terminations on mortality rates in Australia has not yet been estimated. The Western Australian Birth Defects Registry (BDR) records all birth defects that are diagnosed in stillbirths, livebirths and in pregnancies terminated because of a fetal abnormality. All cases on the BDR over the period 1980-98 were categorised into one of eight main birth defect groups and analysed in four time periods to show trends. Linkage provided information on deaths to one year of age, defined as perinatal plus postneonatal deaths. The proportion of terminations for fetal abnormality that would have resulted in a death before one year of age was estimated in two ways. The first method used the proportion of births with a birth defect in each diagnostic category that resulted in a death. The second method involved determination of likelihood of survival to one year of all terminations for fetal abnormality through independent review by two experts. Whilst mortality to one year of age for all birth defects has declined from 4.36/1000 births in 1980-84 to 2.75/1000 births in 1995-98, terminations of pregnancies for fetal abnormalities increased from 1.19/1000 births to 4.70/1000 births. After including the estimated mortality associated with terminations for fetal abnormality, the decline in mortality to one year of age associated with birth defects from 1980 to 1998 changed from a 37% reduction to a 15% reduction based on observed mortality 1980-84, and an 11% increase in mortality based on individual case review, highlighting the importance of considering terminations in mortality analyses.

Abnormalities, Multiple↗

Unsafe abortion: a neglected tragedy. Review from a tertiary care hospital in India.

AIM: With 16% of the world's population, India accounts for over 20% of the world's maternal deaths. The maternal mortality ratio, defined as the number of maternal deaths per 100 000 live births is incredibly high at 408 per 100 000 live births for the country. Abortion has been legalized in India for the past three decades. However, the share of unsafe abortion as a cause of maternal mortality continues to be alarming. The objective of the present study is to identify the magnitude of problem of unsafe abortion in India. METHODS: Emergency gynecologic admissions to a tertiary care center in North India over a 15-year period (1988-2002) were reviewed to evaluate the demographic and clinical profile of patients admitted as a result of unsafe abortion. The records were analyzed with regard to the age group, parity and marital status of the abortion seekers, the indication of abortion, the methods used, qualification of abortion providers, complications and fatality rate. RESULTS: The majority of women who were admitted with diagnosis of unsafe abortion were in the third decade of their lives. They were married, multiparous women living with their spouses. Sixty percent of the women had approached unqualified abortion providers who used primitive methods of pregnancy termination. All the women were admitted with serious complications of unsafe abortions and one-fourth of them succumbed to the complications. CONCLUSION: Unsafe abortion constitutes a major threat to the health and lives of women. This study highlights the need to focus more directly on the needs and preferences of women who seek abortion as well as on the accessibility of contraceptives and skills of the providers of abortion services, in order to improve the quality of abortion care.

Abortion, Induced↗

Sudden coronary death in Glasgow: nature and frequency of acute coronary lesions.

A detailed pathological study of the coronary arteries was carried out on 130 random white subjects (91 male and 39 female) who died suddenly in the Glasgow area. In 30 there was a clearly defined cause of death that was not due to ischaemic heart disease. In eight subjects the cause of death was in doubt. Ninety two of the 130 showed coronary stenosis resulting in a loss of more than 75% of coronary artery cross sectional area and/or acute coronary events with no other cause of death. Of these 92 subjects considered to have died suddenly of ischaemic heart disease, 64% showed plaque rupture and thrombosis which occurred at sites of previous high grades of stenosis. Twenty two subjects had intraluminal thrombosis unrelated to plaque fissuring. Thirty eight (41%) showed histological evidence of recent myocardial necrosis; acute coronary events occurred in 34 of these. There was no correlation between the duration of symptoms before death and the occurrence of acute coronary events. Acute coronary events, mainly in the form of plaque rupture, are a common finding in sudden coronary death when a careful study is made of the whole coronary arterial tree.

Acute Disease↗

Delayed neuronal death and delayed neuronal recovery in the human brain following global ischemia.

The understanding of delayed hippocampal death as a therapeutic window for post-ischemic treatment of the brain has led to numerous investigations focusing upon underlying cellular mechanisms and pharmacological potentials in gerbils and rats. Nevertheless, studies on the occurrence of delayed neuronal death in the human brain have been singular and dealt with only small files of patients. To complement these limited data, in the present study 26 adult patients with a history of a single cardiac arrest were included. Following successful resuscitation, individual survival ranged from less than 1 h to 186 days (mean = 11 days). The severity of the resultant ischemic injury in hippocampus CA1, among Purkinje cells, or in frontal neocortex, respectively, was quantified by direct counting of necrotic neurons. Additionally, hippocampal specimens were immunostained for neuron-specific enolase. The data obtained demonstrate the occurrence of delayed neuronal death in human hippocampus and, in a minor form, in cerebellar Purkinje cells. This is in contrasts to the immediate manifestation of ischemic neuronal necrosis in the neocortex. Unlike previous findings in experimental animals and in humans, the delay of CA1 cell death could be defined as lasting about 7 days following cardiac arrest. Moreover, the immunohistochemical results indicate delayed neuronal recovery in CA1, which in the time course reciprocally corresponds to delayed manifestation of hippocampal neuronal death. Interpretation of the results must consider the lack of information about the exact individual duration of cardiac arrest and resuscitation, as well as missing data concerning pre-ischemic physiological variables.

Adult↗

Fetal assessment based on fetal biophysical profile scoring: experience in 19,221 referred high-risk pregnancies. II. An analysis of false-negative fetal deaths.

The incidence of false-negative fetal death, which is defined as stillbirth unrelated to major anomaly or alloimmunization occurring after a last normal fetal biophysical score, was determined in 19,221 referred high-risk pregnancies. The calculated rate of fetal death after a last normal test was 0.726/1000 (14 deaths), which remained relatively constant despite a progressive increase in tests and patients studied. We conclude that a normal fetal biophysical profile score confers a high probability of perinatal survival.

Amniotic Fluid↗

The ALSFRSr predicts survival time in an ALS clinic population.

OBJECTIVE: To determine whether the Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRSr), a predictor of survival time in ALS clinical trials, predicts survival time in an ALS clinic population. METHODS: The authors prospectively evaluated 267 consecutive patients with ALS at first visit to an ALS clinic using the ALSFRSr and pulmonary function testing. The association of ALSFRSr score at baseline with death or tracheostomy in ALS was examined using Cox proportional hazards models, adjusting for age at baseline, sex, and symptom duration. RESULTS: Of 267 patients with ALS, 103 (39%) reached the endpoint, defined as either death (79 patients) or tracheostomy (24 patients), during a mean follow-up of 1.0 +/- 0.7 years. Among the 103 patients who reached the endpoint during follow-up, 77 (75%) had a baseline ALSFRSr score of less than 38 (the median baseline score of all patients), compared to 53 of 164 (32%) who remained alive without tracheostomy. Patients with a total ALSFRSr score below the median had a 4.4-fold increased risk of death or tracheostomy compared to those who scored above the median (HR: 4.38, 95% CI: 2.79 to 6.86, p < 0.001). Both the total ALSFRSr score at baseline (HR: 0.94, 95% CI: 0.91 to 0.98, p < 0.001) and forced vital capacity at baseline (HR: 0.99, 95% CI: 0.98 to 1.00, p = 0.02) were associated with death or tracheostomy when included in the same Cox model. CONCLUSIONS: In an ALS clinic population, the total Amyotrophic Lateral Sclerosis Functional Rating Scale-revised score at baseline is a strong predictor of death or tracheostomy independently of forced vital capacity and after adjustment for age at baseline, sex, and symptom duration.

Age of Onset↗