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PubMed1996

Immunodeficiency as a component of recognizable syndromes.

Immunodeficiency occurs in numerous genetic syndromes. While it is the dominant manifestation in primary immunodeficiencies, immune deficits may also be seen in a variety of other recognizable syndromes. Immunodeficiency has been reported in 64 such conditions, adding to the 45 recognized primary immunodeficiencies. These uncommon syndromes with immune defects can present with: (a) growth deficiency (11 syndromes with disproportionate or proportionate short stature), (b) specific organ system dysfunction (18 with gastrointestinal, dermatologic, or neurologic abnormalities), (c) inborn errors of metabolism (13), (d) miscellaneous anomalies (10), or (e) chromosome anomalies (12). In most of the disorders, only some of the affected patients have immune defects. However, in 27 syndromes, immunodeficiency is a constant finding. We briefly review the clinical manifestations of each syndrome and delineate the specific associated immune defects. In most syndromes, the connection between the immune and other defects is unknown. Recognition of these conditions involving both the immune and other organ systems may facilitate accurate diagnosis and management as well as yield information regarding genes critical for the development of the involved systems.

Chromosome Aberrations↗

PubMed2003

Percutaneous endoscopic gastrostomy to set up a long-term enteral feeding route in children: an encouraging result.

Percutaneous endoscopic gastrostomy (PEG) is now accepted as the preferred technique to establish long-term enteral feeding. A total of 30 pediatric patients (21 males and 9 females, aged from 5 months to 14 years) underwent PEG in the National Taiwan University Hospital from December 1994 to February 2001. The underlying diseases of the patients receiving PEG were neurological dysfunction ( n=26), gastrointestinal disease ( n=2) and metabolic disorders ( n=2). All patients received intravenous sedation and PEG was performed successfully. Prophylactic antibiotic treatment was given for 1 day. Tube feeding began 48 h after the placement. The Z-score of weight before and 6 months after PEG was -1.54+/-1.74 and -0.98+/-1.46, respectively, which is significant (paired t-test, p<0.0001). Accelerated weight gain was found after PEG. Complications of PEG in our patients included local wound infection ( n=15), gastrocolic fistula ( n=1), pneumoperitoneum ( n=1), dislodgement of tube ( n=6) and tube occlusion ( n=2). Of these patients 12 received button replacement after PEG and the gastrostomy tube was discontinued in 2 patients when they resumed adequate oral intake. Removal of PEG was performed in 2 patients due to complications of gastrocolic fistula and severe dislodgement. Our results encourage the use of PEG as a long-term route for nutritional supply.

Adolescent↗

PubMed1995

Neonatal extracorporeal membrane oxygenation complicated by sepsis. Extracorporeal Life Support Organization.

The onset of sepsis in neonates while on extracorporeal membrane oxygenation (ECMO) may portend adverse results. Nevertheless, ECMO has been used as a therapy in the management of septic conditions. This study assessed morbidity and mortality in neonates in whom septic complications developed while they were on ECMO. Of 5,123 neonates in the Extracorporeal Life Support Organization Registry undergoing ECMO for nonseptic indications, 217 patients had development of septic complications. A multivariate logistic regression analysis that considered 15 pre-ECMO criteria was performed to evaluate outcome. Mortality was higher in the septic group (35% versus 17%; p < 0.002) and ECMO duration averaged 85 hours longer (p < 0.001). Septic neonates had a greater frequency of complications including seizures, gastrointestinal bleeding, renal dysfunction, and metabolic problems (all p < 0.05). Transfusion requirements were doubled. Oxygenator thrombi and hemofilter malfunction occurred more often in septic patients (p < 0.03). New strategies to prevent sepsis and associated thrombotic and metabolic complications may be indicated. A critical reappraisal of continued aggressive support may be warranted when septic complications develop in neonates during ECMO.

Analysis of Variance↗

PubMed1993

Perspectives on lead toxicity.

Lead toxicity causes hematological, gastrointestinal, and neurological dysfunction in adults and children. Symptoms are usually noted with blood lead greater than 1.93 mumol/L. Severe or prolonged exposure may also cause chronic nephropathy, hypertension, and reproductive impairment. Lead inhibits enzymes; alters cellular calcium metabolism; stimulates synthesis of binding proteins in kidney, brain, and bone; and slows nerve conduction. Less severe exposure to lead, designated by blood lead levels of 0.48-0.96 mumol/L, has been implicated in poor pregnancy outcome, impaired neurobehavioral development, reduced stature in young children, and higher blood pressure in adults. Biochemical and systemic effects of high and low level lead toxicity are described. Dust, water, and paint chips are still major sources of lead but lead from folk remedies, cosmetics, food supplements, food preparation utensils, and improperly prepared infant formula has caused epidemic and sporadic severe lead toxicity. Screening for pediatric low level lead exposure requires measurement of blood lead.

Adult↗

PubMed1994

Diarrhea and autonomic dysfunction in a patient with hexosaminidase B deficiency (Sandhoff disease).

The causal factors and the physiopathology of motor diarrhea are still unclear. This case report describes a 60-year-old white man with severe diarrhea for more than 10 years and minor signs of autonomic dysfunction. Extensive investigation showed that small intestinal motility and absorption were normal but that accelerated colon transit precluded water and solute absorption from the large bowel. Orthostatic hypotension, sexual dysfunction, and loss of sweating suggested dysfunction of the autonomous nervous system, which was confirmed by reduced plasma concentrations of norepinephrine and dopamine. Rectal biopsy specimens showed enlarged enteric ganglion cells filled with lipidic material. Levels of total hexosaminidase and hexosaminidase B in plasma, white blood cells, and fibroblasts were decreased, as found in Sandhoff disease. The pedigree of the proband's family showed several affected and heterozygous individuals, detected by examination of total hexosaminidase and hexosaminidase B levels in plasma. Among the five homozygous subjects, three had a clinical picture of diarrhea and orthostatic hypotension since the age of 50. Therefore, hexosaminidase B deficiency should probably be regarded as a cause for dysautonomia; dysfunction of the gastrointestinal tract, manifested by motor diarrhea or esophageal dysmotility, could be the initial and prevalent presentation of dysautonomia.

Autonomic Nervous System Diseases↗

PubMed1993

Posttransfusion graft-versus-host disease in two immunocompetent patients.

Graft-versus-host disease may occur in certain immunocompromised patients after a blood transfusion. The disease is characterized by fever, a skin eruption, gastrointestinal disturbances, liver dysfunction, and bone marrow aplasia. Two cases of fatal graft-versus-host disease are reported. Both patients were immunocompetent and had received transfusions of nonirradiated blood from their children during surgery. The importance of preventing this complication by irradiating blood products given to patients by their first-degree relatives is underscored.

Aged↗

PubMed1997

Initial experience with FK506 (tacrolimus) in pediatric renal transplant recipients.

PURPOSE: The efficacy and safety of the new immunosuppressant agent, FK506 (tacrolimus), was assessed in pediatric renal transplant recipients over a mean 12-month follow-up period. METHODS: Twenty pediatric renal transplant recipients received oral FK506 therapy (0.3 mg/kg/d) in combination with azathioprine (1 to 2 mg/kg/d) and low-dose prednisone as primary therapy (n = 11) or were converted from cyclosporine-based therapy (n = 9) for complications including cyclosporine toxicity (n = 2), acute refractory rejection (n = 4), and chronic rejection (n = 3). Patients were then followed-up prospectively to evaluate effectiveness of therapy and complications. RESULTS: In the primary treatment group, 45% of patients had one or more rejection episodes. Two required OKT3 therapy (18%) for persistent rejection, with one (9%) graft loss at 3 months. All other episodes were treated effectively with FK506 dose adjustment and steroid pulses. Patient and graft survival was 100% and 91%, respectively, at 12 months mean follow-up. In the FK506 conversion group, two teenage girls with intractable acne and hirsutism were converted with complete resolution and no change in renal function. Four patients were converted for acute rejection: two who did not respond to steroid pulse and two who did not respond to both steroids and OKT3. All four grafts were salvaged (mean follow-up, 12 months; mean Creatinine [Cr], 1.1). Three patients were converted for biopsy-proven chronic rejection at 3, 10, and 12 years after transplant (mean Cr, 2.4) with two of three of patients stable with functioning grafts at 1 year after conversion. Complications of FK506 therapy included temporary insulin-dependent diabetes mellitus (10%), neurological complications (25%), renal toxicity (15%), and hypertension (85%). There were no cases of gastrointestinal toxicity, hepatic dysfunction, lymphoproliferative disorders, or life threatening viral infection. All symptoms of toxicity responded to dose adjustment. No patient required conversion from FK506 to other agents. CONCLUSION: This early experience indicates that FK506 in combination with low-dose steroids and azathioprine appears to provide safe and effective immunosuppression in the pediatric age group as a primary agent and may salvage grafts in patients with refractory steroid and OKT3 resistant rejection. Graft and patient survival is comparable to that seen with conventional cyclosporine-based immunosuppression.

Adolescent↗

PubMed2000

Negative relationships between erythrocyte Ca-pump activity and lead levels in mothers and newborns.

Lead poisoning induces hematological, gastrointestinal and neurological dysfunctions. One of the potential mechanisms is the inhibition of calcium-pump (Ca-pump), a transport protein. We investigated the effects of an environmental low lead exposure on Ca-pump activity in 247 mothers and their newborns. Maternal and cord blood, and newborn and mother hair, were sampled at delivery. Geometric means for mother and cord blood lead (Pb-B), and for mother and newborn hair lead (Pb-H), were 6.3 and 4.8 microg/dl, and 1.7 and 1.1 microg/g. Means for mother and cord basal Ca-pump activities were 2,442 and 2,675 nM/mg/hr. Mother enzymatic activity was negatively related to her Pb-B and Pb-H and to the cord Pb-B and newborn Pb-H levels. Newborn enzymatic activity was negatively related to his Pb-H level only. Adjustment for gestational age, child's sex, mother's age at delivery, alcohol, coffee and tea consumption, and smoking habits during pregnancy did not modify these relationships. Our findings support the hypothesis that lead toxicity could be in part mediated by a reduction of Ca-pump activity. This effect could be observed at low environmental exposure, in mothers and newborns.

Adult↗

PubMed1983

The role of intravenous hyperalimentation in intestinal disease.

This article has dealt briefly with intravenous nutrition in intestinal disorders. The indications for its use and techniques of nutritional assessment have been stressed. The use of intravenous hyperalimentation in a few of the more common diseases of the small bowel and colon has been discussed. Every patient with disease of the small or large intestine has some degree of dysfunction in the gastrointestinal tract. In many instances, this functional impairment interferes with normal ingestion or absorption of nutrients and predisposes the patient to malnutrition. The presence of malnutrition increases the morbidity and mortality of surgery and can be reversed by using intravenous hyperalimentation. Those patients with extreme short bowel syndrome secondary to intestinal disease or its parenteral nutrition at home. We stress the importance of a team approach to hyperalimentation. The evolution of a team of nutritional experts will improve the care of the patient and the education of the patient and physician and make nutritional support more readily available to those medical and surgical patients in need.

Anthropometry↗

PubMed2000

Shift work and health.

Night work and rotating shift work disrupt the circadian timing system. This disruption may produce significant deleterious symptoms in some workers. Certain medical conditions may be aggravated by shift-work scheduling, and shift workers are at increased risk of experiencing cardiovascular, gastrointestinal, and reproductive dysfunction. Vulnerable individuals may develop clinical depression when working shifts. Primary care practitioners may intervene by providing medical surveillance and educational programs for shift-working patients and their families.

Humans↗

PubMed1984

Amiodarone: electrophysiologic actions, pharmacokinetics and clinical effects.

Interest in amiodarone has increased because of its remarkable efficacy as an antiarrhythmic agent. The purpose of this report is to review what is known about the electrophysiologic actions, hemodynamic effects, pharmacokinetics, alterations of thyroid function, response to treatment of supraventricular and ventricular tachyarrhythmias and adverse effects of amiodarone. Understanding the actions of amiodarone and its metabolism will provide more intelligent use of the drug and minimize the development of side effects. The mechanism by which amiodarone suppresses cardiac arrhythmias is not known and may relate to prolongation of refractoriness in all cardiac tissues, suppression of automaticity in some fibers, minimal slowing of conduction in fast channel-dependent tissue, or to interactions with the autonomic nervous system, alterations in thyroid metabolism or other factors. Amiodarone exerts definite but fairly minor negative inotropic effects that may be offset by its vasodilator actions. Amiodarone has a reduced clearance rate, large volume of distribution, low bioavailability and a long half-life that may last 2 months in patients receiving short-term therapy. Therapeutic serum concentrations range between 1.0 and 3.5 micrograms/ml. The drug suppresses recurrences of cardiac tachyarrhythmias in a high percent of patients, in the range of 80% or more for most supraventricular tachycardias and in about 66% of patients with ventricular tachyarrhythmias, sometimes requiring addition of a second antiarrhythmic agent. Side effects, particularly when high doses are used, may limit amiodarone's usefulness and include skin, corneal, thyroid, pulmonary, neurologic, gastrointestinal and hepatic dysfunction. Aggravation of cardiac arrhythmias occurs but serious arrhythmias are caused in less than 5% of patients. Amiodarone affects the metabolism of many other drugs and care must be used to reduce doses of agents combined with amiodarone.

Administration, Oral↗

PubMed2004

Renal insufficiency may partly explain chronic anemia in patients awaiting liver transplantation.

In patients with cirrhosis, anemia is common and is likely to be multifactorial, including decreased erythrocyte production, sequestration due to hypersplenism, hemolysis, and increased blood loss from gastrointestinal bleeding. Renal dysfunction is also common in liver disease and this may also cause anemia. However, an association between anemia and renal dysfunction has not been reported in patients with cirrhosis. Our objective was to determine whether anemia in cirrhotic patients is independently related to renal dysfunction. We conducted a retrospective chart review of patients in our institution listed for liver transplantation. We collected simultaneous data on age, hemoglobin, creatinine, albumin, liver enzymes, prothrombin time, and bilirubin. We excluded patients who were hospitalized or deceased to avoid confounding variables. Two hundred eighty-six (female n = 130) patients with a mean age of 52.8 +/- 9.7 (range, 18-73) years were studied. Renal dysfunction (creatinine > 1.2 mg/dL) was present in 55 (19%) patients, and anemia (hemoglobin < 12 g/dL) was seen in 115 (40%) patients. Anemia was more common in patients with renal dysfunction (64 versus 34%; P < 0.001) compared to those with normal renal function. Creatinine, prothrombin time, and bilirubin showed an inverse relationship (all P's < 0.001) with hemoglobin, and albumin showed a positive correlation with hemoglobin (P < 0.001). Multivariate analysis showed that creatinine (OR, 2.4; 95% CI, 1.05-5.3; P = 0.038), prothrombin time (P = 0.026), bilirubin (P = 0.035), and albumin (P = 0.001) were independent predictors of anemia. Renal dysfunction is an important cause of anemia in patients with cirrhosis. The role of erythropoietin in the management of anemia in patients with cirrhosis and renal dysfunction should be explored in prospective studies.

Adolescent↗

PubMed2003

Severe metabolic complications from theophylline intoxication.

Theophylline is commonly used in the treatment of bronchospastic lung disease. In addition to gastrointestinal and cardiac dysfunction, hypokalaemia, lactic and ketoacidosis can complicate theophylline overdose. Clinicians frequently fail to identify theophylline's role when complications develop. A case of an 80-year-old man who developed profound metabolic disturbances while hospitalized is presented. The typical causes of these abnormalities were absent, theophylline levels were elevated, and the patient recovered after theophylline was held. Based on our case and review of the literature, we discuss the reasons why theophylline toxicity is under-recognized, and propose mechanisms for the rare metabolic abnormalities identified in this case. A high index of suspicion for theophylline toxicity should be maintained and it should be considered when unexplained acidosis or hypokalaemia occur.

Acidosis, Lactic↗

PubMed1984

Suppression of appetite by parenteral nutrition in humans.

The effects of parenteral nutrition on appetite during and after therapy are unclear. Previous studies done in animals, as well as in humans, are inconclusive. The purpose of this study was to investigate the effects of parenteral nutrition on voluntary oral intake of food. The study was done on ten stable patients receiving parenteral nutrition for transient dysfunction of their gastrointestinal tract. For each patient, a calorie count of the ingested food was obtained for 3 consecutive days. Parenteral calories were then decreased without the patient's knowledge. A calorie count for 3 more days was obtained following the day of change. The mean daily oral intake was 823 kcal when the mean daily parenteral nutrition intake was 2,902, providing a total of 3,723 kcal. When parenteral nutrition calories were decreased to a mean of 1,550, the mean daily oral intake increased to 1,396. This difference in oral and parenteral calorie intake was statistically significant (P less than .001). It can be concluded from this data that parenteral nutrition decreases voluntary oral intake of food. It is therefore suggested that if the gastrointestinal tract is functionally satisfactory, parenteral nutrition can be rapidly weaned off, provided oral consumption is monitored to assure adequacy.

Adult↗

PubMed2000

Real-time magnetic resonance imaging-guided brachytherapy in the treatment of selected patients with clinically localized prostate cancer.

BACKGROUND AND PURPOSE: A real-time three-dimensional magnetic resonance imaging (MRI)-guided implant technique has been designed and implemented. This report summarizes the dosimetry achieved and the acute morbidity in the first patients. PATIENTS AND METHODS: To date, 43 patients with clinical stage T(1c)N(X)M(0) prostate cancer, serum prostate specific antigen <10 ng/mL, and biopsy Gleason score no higher than 3 + 4 have been treated. The procedure was performed using an open magnet, with axial T1-weighted and fast spin echo images. The prescribed minimum radiation dose to the peripheral zone was 160 Gy. The total activity implanted ranged from 18.8 to 47.5 mCi using 43 to 120 (median 80) (125)I seeds. Dosimetric analyses were performed intraoperatively in real time for the tumor, anterior rectal wall, and prostatic urethra. RESULTS: The percent of the clinical target volume receiving the prescription dose was 89% to 99% (median 96%). Using a conservative estimate of 164 Gy, no more than 9% of the urethral volume exceeded the tolerated dose. Using an estimated tolerated dose of 82 Gy, 30% to 100% (median 68%) of the anterior rectal wall volume was within the dose limit. Thirty-nine patients voided spontaneously within 3 hours of Foley catheter discontinuation, although four patients required recatheterization for a period. No patient reported gastrointestinal or sexual dysfunction during the first postoperative month. CONCLUSION: A real-time MR-guided technique can achieve a minimum of 89% coverage of the tumor volume while maintaining the prostatic urethra and most of the anterior rectal wall below tolerance levels. Acute morbidity was minimal. Further follow-up is needed to ascertain the impact on cancer control and quality of life.

Aged↗

PubMed1997

Multimodal approach to control postoperative pathophysiology and rehabilitation.

Major surgery is still associated with undesirable sequelae such as pain, cardiopulmonary, infective and thromboembolic complications, cerebral dysfunction, nausea and gastrointestinal paralysis, fatigue and prolonged convalescence. The key pathogenic factor in postoperative morbidity, excluding failures of surgical and anaesthetic technique, is the surgical stress response with subsequent increased demands on organ function. These changes in organ function are thought to be mediated by trauma-induced endocrine metabolic changes and activation of several biological cascade systems (cytokines, complement, arachidonic acid metabolites, nitric oxide, free oxygen radicals, etc). To understand postoperative morbidity it is therefore necessary to understand the pathophysiological role of the various components of the surgical stress response and to determine if modification of such responses may improve surgical outcome. While no single technique or drug regimen has been shown to eliminate postoperative morbidity and mortality, multimodal interventions may lead to a major reduction in the undesirable sequelae of surgical injury with improved recovery and reduction in postoperative morbidity and overall costs.

Brain Diseases↗

PubMed1993

Clinical approaches to nutritional support in cancer.

Anorexia and weight loss are frequent complications of cancer and AIDS. Assessment of dietary records and nutritional requirements in patients with decreased food intake and weight loss will assist the dietitian, nurse, or physician in initially addressing the problem. Patients may respond well to nutritional counseling and food supplements, but persistent severe anorexia is common. Various pharmacologic strategies to reverse anorexia and weight loss have been tested, including corticosteroids, anabolic steroids, cyproheptadine, hydrazine sulfate, dronabinol, and megestrol acetate. Dronabinol was recently found to improve appetite in AIDS patients. Megestrol acetate is so far the only agent associated with improvements in appetite and weight in patients with cancer and AIDS. Enteral and parenteral nutrition may be helpful in selected patients with gastrointestinal obstruction or dysfunction, but it is not generally indicated in patients with end-stage disease.

Anorexia↗

PubMed2004

Bilateral total knee replacement using the same anesthetic is not justified by assessment of the risks.

The question of whether simultaneous bilateral knee replacement is associated with an increased risk of perioperative morbidity and mortality remains controversial. There are no true prospective randomized studies that address this question. There is general agreement that the risk is higher for older patients and for those with considerable medical comorbidities, particularly those with a history of cardiac disease. There is no general agreement on the appropriate threshold for age or comorbidities in order to minimize risk. Based on available retrospective data, there is evidence to suggest that there may be some patient selection bias favoring patients with simultaneous bilateral knee replacements; despite this bias, the perioperative risks are higher for these healthier patients. The highest risk for the patient having simultaneous bilateral knee replacement seems to be that of early postoperative mortality followed by the risk of a cardiac event. The risks of thromboembolic, gastrointestinal, and neurologic dysfunction also are increased. These patients also have a higher likelihood of requiring homologous blood transfusions and of requiring posthospitalization transfer to a rehabilitation center. Because of the absence of established patient selection criteria, thresholds for assessment of the increased risks, the patient having simultaneous bilateral replacement faces an increased risk of perioperative mortality and morbidity on a random basis. Patients should be aware of this information when deciding whether to proceed with simultaneous bilateral knee replacement.

Age Factors↗