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Q fever in children.

OBJECTIVE: To describe clinical profiles of Q fever in children. DESIGN: Retrospective study. SETTING: Tertiary teaching hospital. PARTICIPANTS: Thirteen children aged 2 to 14 years, with a mean +/- SD age of 9.6 +/- 3.6 years. SELECTION PROCEDURES: Review of the medical records of all children with Q fever admitted from 1986 to 1990. The diagnosis was made by detection of phase II antibodies to Coxiella burnetii by the complement fixation test. MEASUREMENTS/MAIN RESULTS: Clinical profiles consisted of a self-limited illness characterized by high fever (mean +/- SD, 39.9 degrees C +/- 0.66 degrees C) of 5 to 10 days' duration (mean +/- SD, 7.4 +/- 1.6 days), constitutional symptoms, and mild liver dysfunction. Eleven patients had gastrointestinal manifestations (vomiting and/or abdominal pain). Respiratory symptoms were not prominent. Most patients had normal or low white blood cell counts, and seven showed a relative increase of band forms. Their erythrocyte sedimentation rates ranged from 8 to 23 mm/h. All patients did well without specific therapy for C burnetii. CONCLUSION: In children with the symptoms described above, tests to detect antibodies to C burnetii should be performed.

Adolescent↗

Jejunostomy. A rarely indicated procedure.

Jejunostomy is an alternative for alimentation in patients who cannot be fed orally. Seventy-three patients from the Medical College of Wisconsin Hospitals, Milwaukee, who underwent jejunostomy for gastrointestinal tract obstruction or dysfunction (28 patients), carcinoma (23 patients), neurologic disorders (13 patients), and other indications (nine patients) by the Stamm (46 patients), Witzel (17 patients), and Maydl (nine patients) techniques were studied. Forty-four patients survived and were discharged, while 29 died in the hospital. Fifty-three complications were documented among 34 patients. The jejunostomy was actually used for feeding in only 48 patients, and only 18 were discharged while receiving maintenance enterostomy feedings. Seven patients died as a direct result of complications of the jejunostomy. Jejunostomy is not an innocuous procedure; it carries a substantial risk of death and complications. Jejunostomy should be performed for alimentation only in patients with clear indications and a high potential for long-term use.

Adolescent↗

Are SSRIs better than TCAs? Comparison of SSRIs and TCAs: a meta-analysis.

In this analysis we examined studies of tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) to compare efficacy and drop-out rates. Frequency of reported side effects was also studied. Using Medline, we located 36 clinical trials of TCAs and SSRIs in a double-blind comparison. We performed a meta-analysis on these studies and on a subgroup of 21 studies that had more uniformly defined outcome criteria. The main outcome measures were efficacy for treatment completers and for the intention-to-treat group; drop-out rates due to adverse reactions and lack of efficacy; and reported side effects. Overall, the response rate to treatment for patients who completed a trial was 63.2% for SSRIs and 68.2% for TCAs (P = 0.038). For the intention-to-treat groups, these rates dropped to 48.0 and 48.6% (P, NS), respectively. Significantly more TCA-treated than SSRI-treated subjects dropped out due to either lack of efficacy or adverse reactions (30.0 vs. 24.7%, P = 0.01). Patients taking SSRIs experienced significantly more gastrointestinal problems and sexual dysfunction, whereas treatment with TCAs produced significantly more complaints of sedation, dizziness, and anticholinergic symptoms.

Antidepressive Agents, Tricyclic↗

Sepsis induces increased apoptosis in lamina propria mononuclear cells which is associated with altered cytokine gene expression.

Studies indicate that lymphoid tissue (e.g., thymus, bone marrow, and Peyer's patches) shows evidence of increase apoptosis (Ao, a form of nonnecrotic cell death) during sepsis. However, it is not known if mucosal lymphoid tissue, such as lamina propria (LP), also shows evidence of increased Ao and if so, is this associated with functional changes, i.e., cytokine gene expression in the LP. To examine this, male C3H/HeN mice were subjected to cecal ligation and puncture (CLP) and lamina propria mononuclear cells (LPMC) were harvested at 4 h (early sepsis) or 24 h (late sepsis). Alterations in the cell phenotype as well as Ao (Tunel assay) were determined by three-color flow cytometry. Cytokine gene expression was assessed by multiprobe RNase protection assay. Sham LPMC preparations were found to be 34.4 +/- 2.4% B220(+) (B-cells), while 12.4 +/- 2.1% were CD8(+) (cytotoxic T-cells), 22.0 +/- 0.8% were CD4(+) (helper T-cells), and 6.4 +/- 0.7% were F4/80(+) (macrophages). The frequency of B220(+) (9%* upward arrow) and CD8 (6%* upward arrow) populations increased markedly at 4 h after CLP; however, this increase was not seen at 24 h. The percentage of Ao+ in CD8(+), B220(+), and F4/80(+) cells increased markedly at both 4 and 24 h. CD4(+) cells showed a marked increase in Ao only at 24 h after CLP. When LPMC mRNA expression was examined, a significant increase in IL-2, -10, and -15 gene expression was observed only at 24 h but not 4 h after CLP. Thus, the early phenotypic changes associated with increased Ao may be a reflection of localized immune cell activation in early sepsis contributing to the increased cytokine gene expression seen in late sepsis. This localized activation may contribute to gastrointestinal inflammation and/or immune dysfunction in sepsis.

Animals↗

Clinical characteristics of haemorrhagic fever with renal syndrome in children.

From January 1988 to September 1989, seven patients (4 girls and 3 boys, aged 3-12 years) with haemorrhagic fever with renal syndrome (HFRS) were hospitalised at the University Children's Hospital in Belgrade. In four patients the disease appeared as a family outbreak, the others were sporadic cases. In six patients the clinical presentation was suggestive of HFRS, as they had fever with headache, myalgia, sore throat and gastrointestinal illness followed by renal abnormalities. However, severe haemorrhagic syndrome with petechia, haematoma, haematemesis and melaena was present in one patient only. Renal disease presented as nephritic syndrome and/or acute renal failure. Five patients recovered after 2-3 weeks without sequellae, one patient had decreased renal function 17 months after the start of the disease and the remaining patient died. In six patients the diagnosis of HFRS was confirmed serologically by a significant rise in antibody titres against hantaviruses, while in the patient with the fetal and fulminant course of the disease, the diagnosis was established on the basis of epidemiological and autopsy findings. We suggest that children living in endemic areas who develop an ill-defined, febrile and gastrointestinal disease with renal dysfunction should be evaluated for HFRS.

Animals↗

Diagnosis and treatment of diabetic autonomic neuropathy.

Diabetic autonomic neuropathy (DAN) is associated with a markedly reduced quality of life and poor prognosis. The manifestations of DAN cause multiple symptoms and involve the 1) cardiovascular system: resting tachycardia, reduced heart rate variability and circadian rhythm of heart rate and blood pressure, painless myocardial ischemia/infarction, orthostatic hypotension, exercise intolerance, perioperative instability, sudden death; 2) respiratory system: reduced ventilatory drive to hypercapnia/hypoxemia, sleep apnea; 3) gastrointestinal tract: esophageal motor dysfunction, diabetic gastroparesis, gallbladder atony, diabetic enteropathy, colonic hypomotility, anorectal dysfunction; and 4) genitourinary tract: diabetic cystopathy, erectile dysfunction. Treatment is based on four cornerstones: 1) causal treatment aimed at near-normoglycemia; 2) treatment based on pathogenetic mechanisms; 3) symptomatic treatment; and 4) avoidance of risk factors and complications. Pharmacologic treatment of symptomatic DAN may be difficult, due to limited efficacy and frequent adverse reactions. First-line treatments include midodrine for orthostatic hypotension, prokinetic drugs for gastroparesis, broad-spectrum antibiotics for diabetic diarrhea, and sildenafil for erectile dysfunction. Prior to an adequate symptomatic treatment a thorough risk-benefit estimate, aimed at maintaining the patient's quality of life, is required.

Autonomic Nervous System Diseases↗

Neurogenic bladder. New clinical finding in Legionnaires' disease.

Legionnaires' disease presents with a spectrum of organ involvement including pulmonary, hepatic, gastrointestinal, metabolic, and renal dysfunction. Known neurologic manifestations include hallucinations, delirium, cerebral and cerebellar disturbance, and encephalomyelitis. Clinical and subclinical peripheral neuropathy has been described. This report describes a 51-year-old man with legionnaires' disease complicated by cerebral and persistent cerebellar and brainstem dysfunction, without evidence of direct bacterial invasion of the nervous system. Of particular interest was the development of a flaccid neurogenic bladder, a clinical manifestation not previously described.

Bipolar Disorder↗

Morphometric analysis of the vagus nerve in non-diabetic and ketonuric diabetic Chinese hamsters.

Morphometric analysis of axons from the ventral division of the vagus nerve of ketonuric diabetic Chinese hamsters and age-sex matched non-diabetic controls was performed to determine the frequency distribution and numerical and volume density. Myelinated fibres of diabetics displayed a significant reduction in diameter (P less than 0.001) compared with controls, which was correlated inversely with progressive ketonuria (P less than 0.05). The reduced calibre of myelinated fibres was the result of thin myelin sheaths rather than a reduction in axon diameter. A marked decrease in numerical density (P less than 0.05) and volume density (P less than 0.005) was found in the myelinated fibres of diabetics compared with controls. Non-myelinated axons showed a significant shift to smaller diameter (P less than 0.001) in diabetics, which was correlated inversely with duration of ketonuria (P less than 0.05). Numerical density of non-myelinated axons was increased (P less than 0.01) in diabetic hamsters whereas volume density was comparable in diabetic and control animals. These data provide morphological evidence of impairment in the parasympathetic nervous system which may be a major factor underlying previously reported gastrointestinal and pancreatic islet dysfunction in the diabetic Chinese hamster.

Animals↗

Untreated anorexia nervosa. A case study of the medical consequences.

This case demonstrates the devastating physical sequelae of 30 years of untreated anorexia nervosa. A full array of these consequences occur in this one patient and include the following: malnutrition and hypoproteinemia, electrolyte disturbances, cortical atrophy with hydrocephalus ex vacuo, tricuspid and mitral valvular dysfunction, anemia, impaired lower gastrointestinal motility, delayed gastric emptying, disturbances in the hypothalamic pituitary target organ axes, severe osteoporosis, marked edema, and extreme muscle wasting. Other possible physical sequelae of her anorexia nervosa are discussed. Psychiatrists, as well as other physicians, should be vigilant in diagnosing this illness and treating it as early as possible. This particular patient was in the medical system for numerous admissions and workups over three decades before the correct diagnosis of anorexia nervosa was made.

Aged↗

Safety of Hypericum extract in mildly to moderately depressed outpatients: a review based on data from three randomized, placebo-controlled trials.

RATIONALE: Hypericum extracts have been regarded as antidepressant drugs without specific side effects by patients, medical professionals and researchers alike. Recently there has been discussion about potential interactions between St. John's wort and other drugs. OBJECTIVES: To investigate the tolerability of Hypericum extract by comparing adverse event rates observed during clinical trials with the herbal drug to those observed under placebo and synthetic antidepressants. METHODS: A data review was performed based on the original data of three double-blind, randomised multicenter trials, during which 594 out-patients suffering from mild to moderate depression according to DSM-IV criteria received 3 x 300 mg/day Hypericum extract (WS 5570, WS 5572, WS 5573) or placebo over a double-blind treatment period of 6 weeks. For the polled data from the three trials, the risk ratios and risk differences versus placebo for single and grouped adverse events were determined along with their 95% confidence intervals. The data were inspected for relevant differences between Hypericum extract and placebo and were compared to trials involving the administration of several synthetic antidepressants. RESULTS: For the polled data of the three trials, the percentage of patients with any adverse events under Hypericum extract exposition was comparable to placebo. The drug was also found to be devoid of effects of sedation, anticholinergic reactions, gastrointestinal disturbances and sexual dysfunction often found in patients treated with tricyclic antidepressants or selective serotonin reuptake inhibitors. CONCLUSION: The analysis did not reveal any specific effects of Hypericum extract.

Antidepressive Agents↗

The effect of profound umbilical artery acidemia in term neonates admitted to a newborn nursery.

OBJECTIVE: To determine whether there were immediate adverse effects of an umbilical artery pH < or = 7.0 in term and near-term infants. STUDY DESIGN: All infants triaged to the newborn nursery with an umbilical artery pH < or = 7.0 from May 1993 through April 1994 (n = 37) were prospectively identified; 35 of the 37 infants were enrolled and matched with nonacidemic control infants (n = 35). Organ system dysfunction (neurologic, renal, hepatic, gastrointestinal) was evaluated either clinically or biochemically with selected blood and urine parameters. RESULTS: Acidemic and control groups were similar for pregnancy complications before labor, but acidemic infants were more often delivered by cesarean section (20/35 vs 6/35, p = 0.001). No differences existed between acidemic and control infants in gestational age, birth weight, neurologic evaluations, hearing deficits, feeding tolerance, and hepatic function. The acidemic group had a higher mean serum creatinine than control infants on day 2 of life (0.90 +/- 0.34 vs 0.71 +/- 0.12 mg/dl, p = 0.005) and a greater number of infants with a urine Chemstrip positive for heme (14/35 vs 3/35, p = 0.005). No differences existed between groups in time to first void, urine specific gravity, and number of infants with microscopic hematuria. CONCLUSION: Term and near-term infants born with an umbilical artery pH < or = 7.0 and triaged to the newborn nursery on the basis of a stable appearance in the delivery room do not have clinical manifestations of hypoxia-ischemia in the 48 hours after birth. The higher mean serum creatinine for acidemic compared with control groups is presumably prerenal in origin and results from processes responsible for profound fetal acidemia. Infants with an umbilical artery pH < or = 7.0 and assessed to be clinically well can be treated similar to nonacidemic infants.

Acidosis↗

High-dose vitamin B(6) treatment in West syndrome.

Approximately 10-30% of patients with West syndrome respond to high-dose vitamin B(6) treatment. The response to vitamin B(6) is rapid; seizures disappear within the first 2 weeks of treatment. Mild side effects, such as gastrointestinal symptoms and liver dysfunction, are observed in 40-70%, but these resolve after discontinuation or a reduction of the dosage of vitamin B(6). High-dose vitamin B(6) treatment is useful as a first line agent in treating West syndrome.

Electrocardiography↗

Coping with autonomic neuropathy.

Diabetic autonomic neuropathy, the most common of all the complications associated with diabetes mellitus, is manifested as cardiovascular or gastrointestinal denervation, counterregulatory hormone dysfunction, and genitourinary tract denervation. Its treatment at this time is largely palliative, although there is some indication that control of hyperglycemia, hypertension, and obesity may prevent or delay its development. Both counseling and pharmaceutical approaches are essential to permit the afflicted diabetic patient a reasonably good quality of life.

Autonomic Nervous System↗

The chronic toxicity of inorganic mercury in goats: clinical signs, toxicopathological changes and residual concentrations.

Chronic mercury toxicity was induced in goats by administering mercuric chloride at 100 micrograms/ml in deionized drinking water offered ad libitum for 90 days. Toxic signs of gastrointestinal disturbances and renal dysfunction developed from 43 days onwards without any mortality. The toxicity also induced nephrosis and tubular nephritis; centrilobular necrosis of liver; mild to moderate necrosis in spleen, intestine and lymph node; Zenker's degeneration of cardiac muscles; exudative pneumonia; and pial congestion, oedema and vacuolation in the brain. In addition, hyperaemia, oedema and tissue haemorrhages were evident in most of the organs. The kidneys contained the largest residues of mercury, followed by liver, spleen, intestine, lymph node, skeletal muscles, lungs, heart, brain and the omental fat. The intensity of the cytotoxic changes in the various organs was proportional to the amount of mercury accumulated.

Analysis of Variance↗

Anderson-Fabry disease: clinical manifestations of disease in female heterozygotes.

Anderson-Fabry disease is a rare, X-chromosomal lipid storage disorder caused by a deficiency of lysosomal alpha-galactosidase A. Clinical manifestations of Anderson-Fabry disease include excruciating pain in the extremities (acroparaesthesia), skin vessel ectasia (angiokeratoma), corneal and lenticular opacity, cardiovascular disease, stroke and renal failure, only renal failure being a frequent cause of death. Heterozygote female carriers have often been reported as being asymptomatic or having an attenuated form of the disease. To evaluate the spectrum of clinical signs in heterozygotes, a comprehensive clinical examination was performed on 20 carriers of Anderson-Fabry disease. This revealed that, in addition to the skin manifestation, various other clinical manifestations of the disease are present, including acroparaesthesia, kidney dysfunction, cerebrovascular disease, and gastrointestinal and heart problems. It therefore appears that Anderson-Fabry disease affects both hemizygotes and heterozyotes and therefore should be considered to be an X-linked dominant disease.

Adolescent↗

Survival and therapeutic potential of probiotic organisms with reference to Lactobacillus acidophilus and Bifidobacterium spp.

The present paper provides an overview on the use of probiotic organisms as live supplements, with particular emphasis on Lactobacillus acidophilus and Bifidobacterium spp. The therapeutic potential of these bacteria in fermented dairy products is dependent on their survival during manufacture and storage. Probiotic bacteria are increasingly used in food and pharmaceutical applications to balance disturbed intestinal microflora and related dysfunction of the human gastrointestinal tract. Lactobacillus acidophilus and Bifidobacterium spp. have been reported to be beneficial probiotic organisms that provide excellent therapeutic benefits. The biological activity of probiotic bacteria is due in part to their ability to attach to enterocytes. This inhibits the binding of enteric pathogens by a process of competitive exclusion. Attachment of probiotic bacteria to cell surface receptors of enterocytes also initiates signalling events that result in the synthesis of cytokines. Probiotic bacteria also exert an influence on commensal micro-organisms by the production of lactic acid and bacteriocins. These substances inhibit growth of pathogens and also alter the ecological balance of enteric commensals. Production of butyric acid by some probiotic bacteria affects the turnover of enterocytes and neutralizes the activity of dietary carcinogens, such as nitrosamines, that are generated by the metabolic activity of commensal bacteria in subjects consuming a high-protein diet. Therefore, inclusion of probiotic bacteria in fermented dairy products enhances their value as better therapeutic functional foods. However, insufficient viability and survival of these bacteria remain a problem in commercial food products. By selecting better functional probiotic strains and adopting improved methods to enhance survival, including the use of appropriate prebiotics and the optimal combination of probiotics and prebiotics (synbiotics), an increased delivery of viable bacteria in fermented products to the consumers can be achieved.

Adjuvants, Immunologic↗

Long-Term Complications of Treatment and Causes of Mortality After Hodgkin's Disease.

The majority of newly diagnosed patients are expected to survive Hodgkin's disease because of effective therapies established during past 30 years. Long-term observations from large populations of treated patients have disclosed a variety of late effects of the disease and its therapy have contributed morbidity and excess mortality to Hodgkin's disease survivors. Secondary cancers have continued to accrue, and the risk relative to the general population has increased to 6.4 (95% confidence intervals: 5.5 to 7.3) in updated experience at Stanford University. Risks are significantly elevated for leukemia (primarily after chemotherapy regimens containing alkylating agents); non-Hodgkin's lymphoma; and tumors of the lung, breast, soft tissues, bone, stomach, pancreas, salivary gland, thyroid, and cutaneous melanoma. Early cardiovascular disease has also been observed and numerically exceeds second cancers as a cause of death in patients with early stage Hodgkin's disease (49 v 47 cases). Pulmonary dysfunction, thyroid dysfunction, infertility, psychosocial changes, gastrointestinal problems, soft-tissue changes, alterations in immunity, and risks for infection have also affected some treated patients. As these problems have been recognized, treatment approaches have been modified over the last 10 to 15 years, and early data suggest a decrease in some treatment sequellae.

Journal Article↗

Markers for Patients with Alcohol Problems in an Outpatient General Medicine Clinic.

Our purpose was to determine the correlation among alcohol problems, certain health habits, and hypertension in a general internal medicine outpatient setting. Two-hundred eighty-seven patients who were undergoing complete examinations in a general internal medicine department of a large multispecialty clinic were asked to participate in a "lifestyle survey" interview, which included questions regarding social history, gastrointestinal complaints, anxiety/depression, sexual dysfunction, and the Alcohol Use Disorders Identification Test (AUDIT). Charts were screened for documentation of alcohol problems and the presence of hypertension. Correlations between alcohol problems (defined as an AUDIT score >/=8) and the presence of hypertension were made using chi-square tests for categorical variables and the t test for continuous variables. Of the 287 patients contacted, 12 refused, 3 were ineligible, and 29 had incomplete data precluding analysis, yielding a total of 233 patients (81%) who were included in the analysis. Sixty percent were female, 76% were white, and the mean age was 53 years. The overall prevalence of alcohol problems was 7.3% and less than one-quarter of those patients had chart documentation of an alcohol problem. Thirty percent of those patients had a diagnosis of hypertension. No statistically significant correlation between a positive AUDIT and hypertension was found. Failure to use seat belts (P = 0.020), history of smoking (P < 0.001), alcohol use within 24 hr of the office visit (P < 0.001), and self-reported family history of alcoholism (P = 0.012) were significantly more likely in patients with active alcohol problems. There was no difference in somatic complaints between patients with and patients without alcohol problems. We identified certain health behaviors which served as markers for patients with active alcohol problems in an outpatient setting. Physician diagnosis of alcohol problems (sensitivity of 24% in this study) may be improved with attention to such markers. Despite the known relationship of excess alcohol use and elevations in blood pressure, we found no statistically significant correlation between these variables in our study. Symptomatic concerns of the patient appear to be too nonspecific to distinguish patients with and without alcohol problems.

Journal Article↗