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Clinical and laboratory features and sequelae of deficiency of folic acid (folate) and vitamin B12 (cobalamin) in pregnancy and gynecology.

Classically, deficiency of folic acid (folate) or vitamin B12 (cobalamin) was recognized by the presence of a macrocytic anemia resulting from megaloblastic changes in the bone marrow. A markedly changing paradigm has identified both new mechanisms for altered folate and cobalamin status and new sequelae and clinical interrelationships that include altered mechanisms of absorption, a changing pattern of neurologic deficits, an increased risk of vascular occlusive lesions, and an important relationship with the mechanisms of neoplastic transformation. Several of these newer characterizations relate to issues of neoplasia in the nonpregnant woman and to issues in pregnancy, such as the potential for developmental abnormalities of the fetal nervous system.

Anemia, Megaloblastic↗

Psychological and cardiovascular effects and short-term sequelae of MDMA ("ecstasy") in MDMA-naïve healthy volunteers.

3, 4-methylenedioxymethamphetamine (MDMA, "Ecstasy") is a recreational drug reported to produce a different psychological profile than that of classic hallucinogens and stimulants. It has, therefore, been tentatively classified into a novel pharmacological class termed entactogens. This double-blind placebo-controlled study examined the effects of a typical recreational dose of MDMA (1.7 mg/kg) in 13 MDMA-naïve healthy volunteers. MDMA produced an effective state of enhanced mood, well-being, and increased emotional sensitiveness, little anxiety, but no hallucinations or panic reactions. Mild depersonalization and derealization phenomena occurred together with moderate thought disorder, first signs of loss of body control, and alterations in the meaning of percepts. Subjects also displayed changes in the sense of space and time, heightened sensory awareness, and increased psychomotor drive. MDMA did not impair selective attention as measured by the Stroop test. MDMA increased blood pressure moderately, with the exception of one subject who showed a transient hypertensive reaction. This severe increase in blood pressure indicates that the hypertensive effects of MDMA, even at recreational doses, should not be underestimated, particularly in subjects with latent cardiovascular problems. Most frequent acute somatic complaints during the MDMA challenge were jaw clenching, lack of appetite, impaired gait, and restless legs. Adverse sequelae during the following 24 hours included lack of energy and appetite, feelings of restlessness, insomnia, jaw clenching, occasional difficulty concentrating, and brooding. The present findings are consistent with the hypothesis that MDMA produces a different psychological profile than classic hallucinogens or psychostimulants.

Adult↗

[Neuropsychological sequelae of children treated for brain tumors: evaluation and risk factors].

The analysis of neuropsychological sequelae in children with brain tumors is a major concern in the debate for the definition of the therapeutic strategies. The authors review the recent literature in this field in the light of their own experience at the Gustave-Roussy Institute. Three main risk factors emerge from the analysis: radiation, age and surgical complications. The need for a longitudinal evaluation in these patients is emphasized in order to plan the subsequent appropriate readaptation.

Antineoplastic Agents↗

Neuropathological sequelae of traumatic injury in the brain. An overview.

The identification and interpretation of brain damage resulting from head injury is often not easy. The most obvious structural damage, which is identified post-mortem by neuropathologists, may not be the most reliable alteration with regard to clinico-pathological correlations. For example patients with a fracture of the skull, a severe cerebral contusion or a large intracerebral hematoma that is successfully treated can lead to a complete recovery if no other types of brain damage are present. Thus more subtle forms of pathology, which are often present and some of which can only be identified microscopically, may be more important. It is therefore necessary to get deeper insights into the consequences of brain injury. Though of course not exclusively, this aim can be reached by autopsy. Primary traumatic brain lesions result immediately from mechanical injury. Secondary alterations injuries develop through intracranial and extracranial trauma sequelae, which determine the course and outcome of brain damage. Traumatic brain damage can be classified as focal or diffuse. It may sometimes be difficult to distinguish traumatic from ischemic brain injury. One difference, however, is that the initial events of trauma involve mechanical distortion of the brain. Mechanoporation as traumatic defect in the cell membrane has recently been found to be one of the first steps which leads via ionic influxes to the activation of immediate early genes. Oxygen radicals and cell membrane lipid peroxidation occur also very early. Increased intracellular calcium, activation of phospholipases and calpains furthermore damage the membrane and cytoskeleton and block the axoplasmatic transport, by which delayed cell death can appear. For the description of the extent of traumatically induced brain damage and the possible clinico-pathological correlations it is necessary to take these alterations into consideration as specifically as possible. Neuropathology can contribute to this aim.

Animals↗

Malnutrition sequela on the drug metabolizing enzymes in male Holtzman rats.

The effect of food restriction on the specific activities of the drug metabolizing enzymes (DME) system was studied in Holtzman male rats by comparing DME activities in 90-day-old control rats fed ad libitum (CO), rats fed 40% restricted food (RF) from the gestation period to the day of sacrifice, and recovered rats (rRF) fed 40% restricted food from period of gestation to 45 days of age and then fed ad libitum until the day of sacrifice. In liver, total cytochrome P450 (CYP) of the RF and rRF groups was higher by approximately 50% and 28%, respectively, than in CO rats. Specific activities of individual CYP monooxygenases (MO) such as CYP2B [7-methoxycoumarin demethylase (MOCD)], CYP1A [aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin deethylase (EORD)], and CYP2E [nitrosodimethylamine demethylase (NDMAd)] were 31, 61, 43, and 56% in RF and 16, 36, 26, and 32% in rRF groups, respectively, more than the CO values. Conjugases such as UDP- glucuronosyltransferases with substrates 3-OH benzo(a)pyrene (UGT1) and 4-hydroxybiphenyl (UGT2) and glutathione S-transferase (GST) with substrate 1-chloro-2,4-dinitrobenzene were higher by 72, 69, and 33% in RF and 28, 38, and 24% in rRF groups, respectively. MO activities (MOCD and EORD) were significantly higher in lung, kidney, and intestine: MOCD by 82, 48, and 45% in RF and 40, 25, and 22% in rRF, respectively; and EORD by 84, 77, and 67% in RF and 40, 33, and 28% in rRF, respectively. However, activity of conjugases (UGT1 and GST) were significantly lower (approximately 35-45%) in RF and rRF rats (approximately 20-30%) than in the CO group in above mentioned extrahepatic tissues. These studies indicate that undernourishment during the period of gestation, weanling, and growth and development of microsomal enzymes produces a sequela of events on the DME in hepatic and extrahepatic tissues that cannot return to the control values even when fed ad libitum.

Journal Article↗

Long-term outcomes and risk factor analysis after pneumonectomy for active and sequela forms of pulmonary tuberculosis.

OBJECTIVE: The prevalence of pulmonary tuberculosis remains high in several areas of the world, and pneumonectomy is often necessary to treat the disease. We retrospectively analyzed the morbidities, mortalities, and long-term outcomes after pneumonectomy for the treatment of active tuberculosis or its sequelae. MATERIALS AND METHODS: Between 1981 and 2001, 94 patients underwent either pneumonectomy or pleuropneumonectomy for the treatment of tuberculosis. The patients included 44 males and 50 females and the mean age was 40 (16-68) years. The pathology included destroyed lung in 80, main bronchus stenosis in ten, and both lesions in four. Surgical procedures performed were pneumonectomy in 47, pleuropneumonectomy in 43, and completion pneumonectomy in four. RESULTS: One patient died postoperatively due to empyema. Twenty-three complications occurred in 20 patients: empyema in 15 (including seven bronchopleural fistulae), wound infections in five, and other complications in three. Univariate analysis revealed the presence of empyema, pleuropneumonectomy, prolonged operation time, old age, and intraoperative contamination as risk factors of postpneumonectomy empyema; it also showed that low preoperative FEV(1) and postoperative persistent positive sputum AFB were risk factors of bronchopleural fistula. In multivariate analysis, old age and low preoperative FEV(1) were risk factors of empyema while low preoperative FEV(1), positive sputum acid-fast bacilli, and the presence of aspergilloma were risk factors of bronchopleural fistula. There were 12 late deaths. Actuarial 5- and 10-year survival rates were 94+/-3% and 87+/-4%, respectively. CONCLUSION: Pneumonectomy could be performed with acceptable mortality and morbidity, and could achieve satisfactory long-term survival for the treatment of tuberculosis. In patients with risk factors, special care is recommended to prevent postoperative empyema or bronchopleural fistula.

Adolescent↗

Is Charcot arthropathy a late sequela of osteoporosis in patients with diabetes mellitus?

It is well accepted that Charcot arthropathy is most frequently encountered in the diabetic population. Also well known is the association between diabetes and osteoporosis, even in the absence of overt renal dysfunction. Is it plausible that Charcot arthropathy is a late sequela of osteoporosis in diabetic patients, and if so, can the osteoporosis be treated early, leading to a decrease in the ultimate prevalence of Charcot arthropathy? The objective of this paper is to concisely review the literature detailing the course of Charcot neuroarthropathy and to investigate the links between Charcot arthropathy and osteoporosis among diabetic patients.

Arthropathy, Neurogenic↗

Risk factors and interventions for psychological sequelae in women after miscarriage.

Spontaneous abortion occurs in about one in five pregnancies, and for many women can lead to significant psychological sequelae. This article reviews the literature on the psychological morbidities after pregnancy loss, their risk factors, differences in partner's reactions, potential screening tools and interventions for physicians. The most common reactions women experienced after pregnancy loss were grief, depression, and anxiety, with rates cited of approximately 40%, 12-50%, and 22-41%, respectively. Risk factors for these reactions include having a past psychiatric history, poor social support, no living children, lack of knowledge about miscarriages, and having no explanation for the event. Women's partners also show grief reactions after pregnancy loss, but they grieve less intensely and for a briefer time than women. Men also tend to talk less about their feelings. Women consistently express a desire to have follow-up appointments after a miscarriage, and have a high (75%) show rate when physicians offer them follow-up appointments. The 30-item General Health Questionnaire has good sensitivity and specificity in detecting psychological morbidity after miscarriage. Based on our review we recommend that ob/gyns offer women a follow-up appointment two to three weeks after miscarriage. By using a screening tool such as the General Health Questionnaire and asking about potential risk factors, ob/gyns should be able to effectively identify and refer high risk women to a psychiatric consultant.

Journal Article↗

Adenomyomatous hyperplasia of the papilla of Vater: A sequela of chronic papillitis?

A case of adenomyomatous hyperplasia of the papilla of Vater is described. The lesion presented as a small polypoid tumor projecting into the duodenal lumen, causing obstruction and dilatation of the common bile duct. Serial cross-section of the ampulla showed diffuse thickening of the muscular layer corresponding to Oddi's sphincter, with resulting narrowing of the lumen. Many ductal or glandular components were dispersed within the mucosa and the muscular layer and were admixed with lymphocytes, a few lymphoid aggregates, and fibrosis. Based both on the absence of cellular atypia and the presence of inflammation, fibrosis, and preservation of the normal architecture of the ampulla, we favor the interpretation that this hyperplastic lesion represents a sequela of chronic papillitis. The different diagnoses for this lesion are presented along with a review of the literature.

Adenomyoma↗

Heparin-induced thrombocytopenia with thrombotic sequelae: a review.

Heparin-induced thrombocytopenia (HIT) occurs in 1-5% of patients treated with heparin. The pathogenesis involves the formation of antibodies to heparin-platelet factor 4 complexes, and the major clinical sequelae are thrombotic. Diagnosis is based on a combination of clinical and laboratory data. Treatment consists of stopping heparin, but, insofar as the risk of thrombosis remains high, treatment by alternative antithrombotic agents is indicated. Most clinical experience has been with danaparoid sodium and hirudin. The use of low-molecular-weight heparins (LMWH) in subsequent HIT episodes has been described, but is not recommended, especially with the introduction of new agents, such as oral thrombin inhibitors and pentasaccharides, which are hoped to reduce the use of heparins and the occurrence of HIT.

Animals↗

Severe bronchopulmonary dysplasia increases risk for later neurological and motor sequelae in preterm survivors.

Preterm children who develop severe chronic lung disease may be developmentally compromised by exposure to hypoxic episodes. This study aims to determine if children with severe bronchopulmonary dysplasia (BPD) who required home oxygen therapy were at greater risk for neurological and motor deficits at school age than preterm peers without BPD. This study evaluated 27 subjects with BPD and 27 preterm control infants matched for gestational age, birthweight, sex, and year of birth at a mean age of 9.9 years (2.0 SD) using standardized neuromotor outcome measures. Pair-matched comparisons and regression analyses were used to determine if subjects with BPD were at increased risk for neuromotor sequelae. Neurological abnormalities, including subtle neurological signs, cerebral palsy, microcephaly, and behavioral difficulties were highly prevalent in the BPD group (71% compared with 19% in control group, P<0.005). Over half the BPD cohort had difficulties in gross and/or fine motor skills. There were significant differences in postural stability between groups. Duration of hospitalization and home oxygen treatment, and decreased lung function at school age, markers of severity of illness, correlated with motor outcomes. The findings underline the importance of preventing the cardiorespiratory complications associated with chronic lung disease to minimize disability in preterm children. For children with severe BPD, better recognition and subsequent remediation of neuromotor impairments that manifest at school age may help maximize their functional potential.

Bronchopulmonary Dysplasia↗

Pyopneumothorax--a rare sequelae of retropharyngeal abscess.

A case of massive pyopneumothorax as a rare sequelae of retropharyngeal abscess following fish bone ingestion is reported. An initial attempt at removal of the fish bone in the oesophagus using the fibroptic oesophagoscope was unsuccessful, causing failure of its removal and the development of this rare and potentially fatal complication. The intercommunication of the retropharyngeal space with other spaces of the neck and thorax that allow this and most other complications to occur is described. Rigid endoscopes are the instrument of choice in retrieving sharp foreign bodies in the oesophagus.

Abscess↗

Psychological sequelae of female sterilization: short-term outcome in a prospective controlled study. A report from the UK Field Research Centre of a WHO collaborative project.

Healthy multiparous women having elective interval (N = 69) or postpartum (N = 69) sterilization were interviewed pre-operatively and 6 weeks and 6 months post-operatively, using standardized instruments. They did not differ significantly from control samples of comparable non-sterilized women with respect to mental state (Present State Examination) or subjectively-assessed mental or physical health or abdominal pain. More sterilization subjects than control subjects reported subjectively experienced improvement in sexual satisfaction at the later follow-up. Reports of poor physical health and abdominal pain increased over time within both the sterilization and the control groups. Reports of adverse effects at follow-up were often associated with higher PSE scores initially. Regrets and wish for reversal were rare and were also associated with higher initial PSE scores. Since the adverse effects were more common among postpartum subjects, it is suggested that subjectively experienced sequelae of sterilization may sometimes be attributable to 'normal' postnatal events.

Abdomen↗

A prospective study of children with head injuries: II. Cognitive sequelae.

A 2 1/4-year prospective study of children suffering head injury is described. Three groups of children were studied: (a) 31 children with 'severe' head injuries resulting in a post-traumatic amnesia (PTA) of at least 7 days; (b) an individually matched control group of 28 children with hospital treated orthopaedic injuries; and (c) 29 children with 'mild' head injuries resulting in a PTA exceeding 1 hour but less than 1 week. Individual psychological testing was carried out as soon as the child recovered from PTA, and then again 4 months, 1 year, and 2 1/4 years after the injury. A shortened version of the Wechsler Intelligence Scale for Children (WISC), the Neale Analysis of Reading Ability and a battery of tests of specific cognitive functions were employed. The mild head injury group had a mean level of cognitive functioning below the control group, but the lack of any recovery; during the follow-up period indicated that the intellectual impairment was not a consequence of the injury. In the severe head injury group, the presence of cognitive recovery and a 'dose-response' relationship with the degree of brain injury showed that the intellectual deficits were caused by brain damage. Some degree of cognitive impairment was common following head injuries giving rise to a PTA of at least 2 weeks. Conversely no cognitive sequelae, transient or persistent, could be detected when the PTA was less than 24 hours. The results were less consistent in the 1-day to 2-week PTA range, but the evidence suggested that a broadly defined threshold for impairment operated at about that level of severity of injury. Timed measures of visuo-spatial and visuo-motor skills tended to show more impairment than verbal skills but otherwise there was no suggestion of a specific pattern of cognitive deficit. Recovery was most rapid in the early months after injury, but substantial recovery continued for 1 year with some improvement continuing n the second year in some children, especially those with the most severe injuries. Age, sex and social class showed no significant effects on the course of recovery.

Achievement↗

A prospective study of children with head injuries: III. Psychiatric sequelae.

A 2 1/4-year prospective study of children suffering head injury is described. Three groups of children were studied: (a) 31 children with 'severe' head injuries resulting in a post-traumatic amnesia (PTA) of at least 7 days; (b) an individually matched control group of 28 children with hospital-treated orthopaedic injuries; and (c) 29 children with 'mild' head injuries resulting in a PTA exceeding 1 hour but less than 1 week. A retrospective assessment of the children's pre-accident behaviour was obtained by parental interview and teacher questionnaire immediately after the accident and before the behavioural sequelae of the injury could be known. Further psychiatric assessments were undertaken 4 months, 1 year and 2 1/4 years after the initial injury. The mild head injury group showed a raised level of behavioural disturbance before the accident but no increase thereafter. It was concluded that head injuries resulting in a PTA of less than 1 week did not appreciably increase the psychiatric risk. By contrast, there was a marked increase in psychiatric disorders following severe head injury. The high rate of new disorders in children with severe head injuries who were without disorder before the accident, together with the finding of a dose-response relationship with the severity of brain injury, indicated a causal relationship. However, the development of psychiatric disorders in children with severe head injuries was also influenced by the children's pre-accident behaviour, their intellectual level, and their psychosocial circumstances. With the exception of social disinhibition and a slight tendency for the disorders to show greater persistence over time, the disorders attributable to head injury showed no specific features.

Amnesia↗

Neuropsychological sequelae of obstructive sleep apnea-hypopnea syndrome: a critical review.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a well-recognized clinical sleep disorder that results in chronically fragmented sleep and recurrent hypoxemia. The primary daytime sequelae of the disorder include patient reports of excessive daytime sleepiness, depression, and attention and concentration problems. It has been well established that OSAHS negatively impacts certain aspects of cognitive functioning. The primary goals of this article are to (1) clarify the pattern of cognitive deficits that are specific to OSAHS; (2) identify the specific cognitive domains that improve with treatment; and (3) elucidate the possible mechanisms of cognitive dysfunction in OSAHS. At the conclusion of the paper, we propose a potential neurofunctional theory to account for the etiology of cognitive deficits in OSAHS. Thirty-seven peer-reviewed articles were selected for this review. In general, findings were equivocal for most cognitive domains. Treatment, however, was noted to improve attention/vigilance in most studies and consistently did not improve constructional abilities or psychomotor functioning. The results are discussed in the context of a neurofunctional theory for the effects of OSAHS on the brain.

Attention↗

Neurologic sequelae of treatment of primary CNS lymphomas.

Novel efficient and aggressive treatment protocols for primary CNS lymphomas have resulted in an increasing number of long term survivors. Follow up data show that in a substantial fraction of these patients, treatment benefits are overshadowed by neurotoxic sequelae. Neurotoxicity especially affects the older age group, presenting as cognitive dysfunction, ataxia or dementia as a consequence of leukoencephalopathy and brain atrophy. The combination of radiotherapy and chemotherapy seems to be particularly hazardous, though data are too sparse to draw any definite conclusions yet. Long term follow up of patients included in clinical studies therefore should not only evaluate survival or time to tumour progression, but also serial neuropsychometric evaluation and quality of life assessment.

Aged↗

Electrical injury and lightning injury: a review of their mechanisms and neuropsychological, psychiatric, and neurological sequelae.

Exposure to electrical current via industrial or residential accidents or lightning strikes is a serious and growing concern in today's medical community. The sequelae that result are referred to as electrical injury (EI) or lightning injury (LI). The relevant principles in electricity are reviewed with particular attention given to their damaging capabilities on the body. Specific neuropsychological, psychiatric, and neurological signs and symptoms as well as objective measures of psychological and neuropsychological functioning and brain imaging in victims of EI and LI, are reviewed from past research. Important issues relevant to researchers in the field are discussed. Finally, the role that neuropsychology might play in this area is outlined.

Brain Injury, Chronic↗