Primary subacute epiphyseal osteomyelitis caused by Mycobacterium species in young children: a modern diagnostic approach.

Primary epiphyseal subacute osteomyelitis (PESAO) caused by Mycobacterium species in young children is poorly recognized. We aimed to define the spectrum of this uncommon condition and to propose a novel diagnostic approach. We performed a systematic review of the literature on the PubMed website by selecting all reports of isolated infantile PESAO caused by Mycobacterium species since 1975. We identified 350 citations, of which 174 were assessed for eligibility based on title and abstract. The full text of 81 eligible citations was screened, and relevant data of 15 children under 4 years of age with mycobacterial PESAO were extracted. These data were pooled with those from our Institution. Data from 16 children were reviewed. The median age was 16 ± 7 months and the male:female ratio 1.7. The knee was the most common infection site (94%). The diagnosis of mycobacterial disease was delayed in all cases (range, 2 weeks to 6 months), and initially presumed by histology in 15 children (94%). Microbiologically proven diagnosis was confirmed by bone cultures in 8 of the 15 children (53%), and by specific PCR in 2 of the 3 culture-negative bone specimens (67%). Three children experienced long-term orthopedic complications despite surgical drainage and prolonged antimycobacterial regimens. All recently reported cases came from high-burden tuberculosis areas. Mycobacterium species contribute to the burden of infantile PESAO in endemic tuberculosis areas and may cause growth disturbances. We argue in favor of the early recognition of mycobacterial disease by specific molecular assays in children with infantile PESAO living in high-burden areas.

Thiamine deficiency in patients with B-chronic lymphocytic leukaemia: a pilot study.

Malignancy associated primary thiamine deficiency has been documented in several experimental tumours, sporadic clinical case reports, and in a number of patients with fast growing haematological malignancies. Thiamine status was assessed prospectively in 14 untreated B-chronic lymphocytic leukaemia (CLL) patients, and in 14 age matched control patients with non-malignant disease. Patients with any known cause of absolute, relative, or functional thiamine deficiency were excluded. High (>15%) thiamine pyrophosphate effect (TPPE), indicating thiamine deficiency, was found in five out of 14 CLL patients (35.7%) and in none of the controls (p=0.057). Mean (SD) TPPE in the thiamine deficient patients group was 21.6 (3.4)%. In all the patients, thiamine deficiency was subclinical. No correlates for the thiamine deficiency have been found save for an increment of more than 20% in the total leucocyte count over the preceding three months, which was found in all five thiamine deficient patients compared with only one of the nine non-thiamine deficient CLL patients. Thus, CLL patients may be prone to develop primary thiamine deficiency possibly promoted by the increased leucocytes span, which may increase thiamine consumption. Since even subclinical thiamine deficiency may be detrimental to the patient's clinical course, and in view of the theoretical danger of thiamine promoted tumour cell proliferation, further large scale studies are warranted to confirm this observation, and to elucidate the issue of thiamine supplementation to CLL patients.

Propafenone-induced ataxia: report of three cases.

Propafenone is an effective antiarrhythmic drug used widely for the treatment of supraventricular and ventricular arrhythmias. Although it is generally well tolerated, 30 to 45% of patients may experience adverse cardiac effects. In 15 to 20% of patients, adverse effects may involve other organ systems. A wide variety of adverse central nervous system effects have been reported in association with propafenone; dizziness is the most common. Ataxia caused by propafenone has been reported to the pharmaceutical companies and drug monitoring agencies, but has not been well described or emphasized in the medical literature. We describe 3 elderly patients with moderate to severe ataxia that occurred while they were taking propafenone.

Neuropsychiatric problems in 2,500 long-term young travelers to the tropics.

BACKGROUND: The prevalence and features of travel associated neuropsychiatric problems (NPP) and their relation to previous psychological consultations, antimalarials and recreational drug use have not been adequately studied. METHODS: A two-phase postal and telephone survey has been conducted among 2,500 young travelers to tropical countries. We measured the rate and duration of NPP, characterized their features, and their association with previous psychological profiles, itinerary, type of travel, consumption of recreational drugs, and malaria prophylaxis. RESULTS: First phase: Out of 1,340 respondents, 151 (11.3%) indicated that they had NPP during travel, in contrast with 2.3% who needed psychological consultation before travel (p<.001). Second phase: 117 of 151 responded to the study questionnaire. The mean age of the respondents was 24.4 years, 54.7% were female, and the mean stay abroad was 5.3 months. The most common NPP were sleeping disturbances (52.1%), fatigue (48.7%) and dizziness (39.3%). Thirty-three travelers (2.5%) had severe symptoms, and 16 (1.2%) had symptoms lasting more than 2 months. Seven travelers had pure or mixed depressive symptoms. Consumption of recreational drugs was admitted by 22.2%. Mefloquine was used significantly more often by those who suffered NPP, than by the entire cohort (98.2% vs. 70.7%; p<.001). CONCLUSIONS: Long-term travel to the tropics was associated, in this cohort, with a considerable rate of neuropsychiatric symptoms. The majority of the responding travelers were females, used mefloquine as prophylaxis, and at least one fifth used recreational drugs.

Severe life-threatening hyponatremia during paroxetine therapy.

Hyponatremia secondary to the syndrome of inappropriate secretion of antiduretic hormone (SIADH) is an uncommon complication of treatment with the antidepressants the selective serotonin reuptake inhibitors (SSRIs). These effective anti-depressant agents are becoming widely used because of their favorable side effect profile and their safety in overdose. Although most reports have implicated fluoxetine in causing hyponatremia, there have also been a few reports of hyponatremia associated with paroxetine. We describe an elderly patient with severe life-threatening hyponatremia in association with paroxetine therapy. The present case and the others previously reported emphasize the need for greater awareness of the development of this serious and potentially fatal complication, and suggest that serum sodium concentration should be measured periodically in elderly patients soon after they start taking any agent of the SSRIs, especially during the first 2 to 4 weeks of treatment.

Phenytoin-folic acid interaction: a lesson to be learned.

A case of a patient who developed symptomatic phenytoin-induced folic acid deficiency is reported. Folate supplementation of 5 mg/d was followed by a decrease of serum phenytoin concentration to a subtherapeutic level with a breakthrough seizure. Estimation of phenytoin's Km-Vmax Michaelis-Menten pharmacokinetic parameters in this patient demonstrated that folate supplements indeed caused a significant decrease in the Km value. This decrease correlates with a greater affinity of the metabolizing hepatic enzymes for the drug, and hence, with the resultant increase in phenytoin's metabolism and decrease of its serum concentration and anticonvulsive effect. In an era of increasing knowledge of folate's pivotal role in various diseases, we call attention to this drug-vitamin interaction, and to the previously suggested recommendation that folate supplementation should be initiated whenever phenytoin therapy commences. Because folic acid dosages as low as 1 mg/d may perturbate phenytoin's metabolism, smaller deficiency preventive doses may be the advisable allowance for phenytointreated patients with normal pretreatment folate levels. This suggestion must be confirmed by a prospective study in a large cohort of patients.

Urinary thiamine excretion in the rat: effects of furosemide, other diuretics, and volume load.

Long-term furosemide therapy is associated with increased urinary loss of thiamine. To examine the mechanism of furosemide-induced urinary thiamine loss, we measured urinary excretion of thiamine in rats in response to increasing doses of furosemide, acetazolamide, chlorothiazide, amiloride, mannitol, and extracellular fluid (ECF) volume loading by saline infusion. All animals were in normal thiamine balance as reflected by a thiamine pyrophosphate effect (TPPE) of 2.25% +/- 0.60% (mean +/- SEM), and all had normal renal function. Urinary flow increased in response to diuretic administration in a dose-dependent manner, reaching (mean) peak urinary flow rates of 283 to 402 microL/min. Fractional excretion of sodium (FE(Na)) exhibited the same pattern, reaching peak values of 12.3% to 23.2%. Urinary thiamine excretion increased in proportion to the incremental doses of diuretic agents, reaching (mean) maximal values of 7.44 to 9.34 pmol/min, with no significant difference (P = .11) between the various diuretics tested nor in response to saline loading. None of the diuretics tested differed in the effect on thiamine excretion, which was clearly flow dependent and only partially related to fractional sodium excretion. Urinary flow rate, being the single significant predictor, explained 78% (R2 = 0.78) of the variability in thiamine excretion rates. These findings indicate that urinary thiamine loss is caused by a nonspecific, flow-dependent mechanism common to all of the diuretics tested.

Resource partition history and evolutionary specialization of subunits in complex systems.

Specialization for part of the resources available is a common adaptation leading to diversification in biological systems. In complex ecological communities, the history of diversification of parts of a system correlates with the structure of the system in present times. Abundances and sequences of resource partition of species expected by a sequential broken stick model are compared with observed abundances of species and their sequences of evolutionary divergence. Where resources are abundant, first resource partitions correspond to most ancient speciations, and last to recent speciations. The inverse is true when resources are scarce, agreeing with the occupation of extreme habitats by recent species. Diverging species seem to specialize by dividing the niche of common ancestors. Similar trends exist inside genera as well as between families, suggesting similar patterns in diversification and specialization at other levels of biological organization, such as evolution of functional complexes of macromolecules and organs embryogenesis.

Effect of environmental complexity on salt-adaptation in Sorghum bicolor.

Individual plants of Sorghum bicolor mature different adaptive reactions to salinity. The positive correlation between the frequency of specific reactions and the tolerance level of plants with that specific reaction results from adaptive determinism (AD). The effect of complexity in environmental conditions on AD in plants adapting for the first time to salinity, A0, and in their offspring A1 was compared. Environmental complexity increases when uncontrolled factors besides salinity affect plants. The diversity of reactions of plants correlates positively with environmental complexity. AD correlates negatively to environmental complexity in A1. In contrast, environmental complexity has no effect on AD in A0. A1 are more tolerant to salinity than A0: A1 inherited adaptive information. The likelihood that A1 plants are exposed to the same uncontrolled factor as their parent is low, and so the decrease of AD in A1 due to environmental complexity suggests that: (1) the information inherited is specific to saline conditions; (2) AD results mainly from inherited pre-existing information; plants react as informatively closed systems: saline conditions trigger the expression of an adaptive, pre-existing program. For A0, conclusions are: (1) the adaptive reaction is not an expression of pre-existing information; (2) AD emerges during the adaptation process: the environment imprints adaptively the plant's development. In this case, plants react as open systems in terms of information.

[Gentamycin distribution volume in a mechanically ventilated patient-- pharmacokinetic and clinical aspects].

Mechanical ventilation (MV) of more than 32 hours may alter the gentamycin pharmacokinetic profile by increasing its volume of distribution (VD). As a result, the standard garamycin dosage regime has to be adjusted in order to obtain an adequate peak serum concentration, which is well correlated with the efficacy of garamycin therapy. Garamycin is a water-soluble drug with negligible binding to plasma albumin, so its VD approximates the volume of extra-cellular fluid, which may be expanded by MV. MV-related fluid retention is mediated via various homeostatic compensatory systems. They are activated to combat the decrease in cardiac output and central blood volume caused by MV, due to the increase in airway and intrathoracic pressure. These phenomena are more prominent during prolonged ventilation, PEEP or C-PAP ventilation, and in previously hypovolemic patients. Patients requiring MV for more than 32 hours had an average garamycin VD of 0.36 L/Kg compared with the mean VD of 0.25 L/Kg in normal adults. In the patient presented, a similar change in garamycin VD was seen, while conventional doses given during MV failed to reach suitable clinical peak levels.

Transmission of acquired adjustments to salinity in Sorghum bicolor.

Previous studies showed that exposure of eight-day-old Sorghum bicolor for three weeks to sublethal salinity induces an increase in salinity tolerance, called physiological adaptation (A). During A, plants of a same population differ in reaction and tolerance to salinity. Tolerance levels of the reaction types depend on environmental conditions besides salinity. Reactions observed most frequently in an experiment have generally highest tolerance levels. This phenomenon is defined adaptive determinism (AD). In this study, the relationship between a potential source of the information subjacent to AD and AD itself is analysed in plants first exposed to salt-inducing A. When the reaction types are close variations of one reaction mode. AD is highest. This relationship is inversed in progeny of adapted plants. Results suggest that information relevant to AD is transmitted to the progeny of adapted plants, and that adaptive information is created during A in plants first exposed to adaptation inducing treatment.

Drug-induced tinnitus and other hearing disorders.

Tinnitus and hearing loss, both reversible and irreversible, are associated both with acute intoxication and long term administration of a large range of drugs. The mechanism causing drug-induced ototoxicity is unclear, but may involve biochemical and consequent electrophysiological changes in the inner ear and eighth cranial nerve impulse transmission. Over 130 drugs and chemicals have been reported to be potentially ototoxic. The major classes are the aminoglycosides and other antimicrobials, anti-inflammatory agents, diuretics, antimalarial drugs, antineoplastic agents and some topically administered agents. Prevention of drug-induced ototoxicity is generally based upon consideration and avoidance of appropriate risk factors, as well as on monitoring of renal function, serum drug concentrations, and cochlear and auditory functions before and during drug therapy. Ototoxicity, although not life-threatening, may cause considerable discomfort to patients taking ototoxic drugs, and in some cases drug discontinuation may be necessary to prevent permanent damage. Much research has been performed to investigate the causes and mechanisms of ototoxicity, to try to prevent this complication. Despite these efforts, ototoxicity still occurs, and there is much work to be done in order to understand the mechanism of ototoxicity of different drugs and to prevent hearing loss and tinnitus in the future.

Improved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide therapy.

PURPOSE: We have previously found thiamine (vitamin B1) deficiency in patients with congestive heart failure (CHF) who had received long-term furosemide therapy. In the present study, we assessed the effect of thiamine repletion on thiamine status, functional capacity, and left ventricular ejection fraction (LVEF) in patients with moderate to severe CHF who had received furosemide in doses of 80 mg/d or more for at least 3 months. PATIENTS AND METHODS: Thirty patients were randomized to 1 week of double-blind inpatient therapy with either i.v. thiamine 200 mg/d or placebo (n = 15 each). All previous drugs were continued. Following discharge, all 30 patients received oral thiamine 200 mg/d as outpatients for 6 weeks. Thiamine status was determined by the erythrocyte thiamine-pyrophosphate effect (TPPE). LVEF was determined by echocardiography. RESULTS: TPPE, diuresis, and LVEF were unchanged with i.v. placebo. After i.v. thiamine, TPPE decreased (11.7% +/- 6.5% to 5.4% +/- 3.2%; P < 0.01). LVEF increased (0.28 +/- 0.11 to 0.32 +/- 0.09; P < 0.05), as did diuresis (1,731 +/- 800 mL/d to 2,389 +/- 752 mL/d; P < 0.02), and sodium excretion (84 +/- 52 mEq/d to 116 +/- 83 mEq/d, P < 0.05). In the 27 patients completing the full 7-week intervention, LVEF rose by 22% (0.27 +/- 0.10 to 0.33 +/- 0.11, P < 0.01). CONCLUSIONS: Thiamine repletion can improve left ventricular function and biochemical evidence of thiamine deficiency in some patients with moderate-to-severe CHF who are receiving longterm furosemide therapy.

Adaptive determinism during salt-adaptation in Sorghum bicolr.

During adaptation to salinity, plants of Sorghum bicolor showed malformations affecting the leaves in development (DPL). At the end of the adaptation process, the plants were regrouped according to their pattern of DPL response. The distribution of the plant population in different patterns depended on environmental conditions. However, a positive relationship between the frequency of a pattern and its rate of development has been found. Similarly, a negative relation between the frequency of a pattern and the rate of senescence for the same pattern has been observed. The results reveal the existence of an orientation of the plant response towards the patterns with highest developmental rate and lowest rate of senescence. This property is defined as 'adaptive determinism'. Results indicate that the NaCl acts as a trigger for adaptation to a whole range of environmental perturbations. This suggests that adaptation to salinity is not a pre-programed response of the plants, and may be related to learning processes occurring in animals.

[Digoxin intoxication due to unadjusted loading dose in renal failure].

We describe a case of digoxin intoxication due to an unadjusted loading dose in a patient with renal failure. The importance of individual calculation of the digoxin dosing regimen in patients with renal failure is reemphasized. The volume of distribution of digoxin decreases significantly in chronic renal failure, due to decreased tissue binding in the uremic state. Accordingly, not only the digoxin maintenance dose, but the digoxin loading dose as well must be adjusted in this condition.

Computer assisted design of a theophylline dosing regimen in acute bronchospasm: serum concentrations and clinical outcome.

The effect of intravenous theophylline on the outcome of inhospital treatment of acute bronchospasm has been assessed, comparing the results achieved by computer-assisted dosing, designed to achieve and maintain a serum theophylline level of 16 micrograms.ml-1 (10 patients) with those of unaided physicians (15 control patients). The outcome measures compared were clinical improvement, peak expiratory flow rate and serum theophylline concentration. Loading doses of theophylline in the control and computer groups were: 167 and 437 mg, respectively. Initial serum theophylline concentrations, measured 20 min after the loading dose, were 13.6 and 17.0 micrograms.ml-1 in the control and computer groups, respectively. In patients who had not received theophylline prior to admission, loading doses and initial concentrations were: 200 mg and 9.4 micrograms.ml-1 in the control group (n = 5) versus 613 mg and 15.7 micrograms.ml-1 in the computer group (n = 4), respectively. During maintenance therapy, serum theophylline concentrations were kept in the therapeutic range (10-20 micrograms.ml-1) throughout 51% and 77% of the hospitalisation period, in the control and computer groups, respectively. There were no differences between the two groups in the rate or extent of clinical improvement or in change in peak expiratory flow rate. The computer assisted theophylline dosing regimen outperformed that of the unaided physicians in achieving and maintaining therapeutic serum theophylline concentrations in acute bronchospasm. There was no correlation between clinical outcome and serum theophylline concentration, but this may have been due to the small sample size and modest difference in serum theophylline between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)