HTLV-III infection after bone marrow transplantation

We prospectively documented the development of a fatal, secondarily acquired severe immunodeficiency in a 19-year-old man who underwent uncomplicated bone marrow transplantation. He had no graft v host disease (GVHD) and had normal recovery of his immune system as determined by lymphocyte phenotyping, mitogenic responses of his peripheral blood lymphocytes, and his ability to secrete immunoglobulin. This alteration in immunity was associated with the acquisition of antibody to HTLV-III. His only risk factor for the development of HTLV-III infection was the transfusions he had received during the transplant and recovery period. Two of his 54 transfusions were from an asymptomatic individual at high risk for acquired immunodeficiency syndrome (AIDS), who was subsequently found to be seropositive for anti-HTLV-III and from whom HTLV-III was isolated. The loss of immunocompetence in patients without chronic GVHD disease is unusual, and our data support the view that this patient's immunodeficiency was due to HTLV-III. When bone marrow transplant recipients without chronic GVHD develop late opportunistic infections, consideration should be given to transfusion-associated AIDS.     

Mutagenicity of 2-amino-3-methylimidazo[4,5-f]quinoline in human lymphoblastoid cells

2-Amino-3-methylimidazo[4,5-f]quinoline (IQ), a heterocyclic aromatic amine that has been identified in cooked meats and cigarette condensates, is mutagenic in human lymphoblastoid TK6 cells at the thymidine kinase and hypoxanthine-guanine phosphoribosyl transferase (hprt) loci. Treatment of the cells with IQ following activation with either an exogenous metabolizing mixture (S9) or following photoactivation of the azido-derivative of IQ (N3-IQ) showed that the photolytic-derivative of N3-IQ was more active. This observation is consistent with other reports that indicate that the weak mutagenicity of IQ in mammalian cells is caused by the lack of enzymes required for the ultimate activation of the compound within the cells. Two DNA adducts were found by 32P-post-labelling in the cells treated with the photoactivated N3-IQ. The major adduct was identified as N- (deoxyguanosin-8-yl)-2-amino-3-methylimidazo[4,5-f]quinoline (dG-C8-IQ) and the minor adduct as 5-(deoxyguanosin-N2-yl)-2-amino-3- methylimidazo[4,5-f]quinoline (dG-N2-IQ). The ratio of the dG-C8IQ to the dG-N2-IQ adducts was approximately 3:1 and did not significantly change in cultures treated with different concentrations of the mutagen. Approximately 50% of the adducts were removed 9 h after treatment with IQ and <10% of these adducts remained after 24 h. There was no significant preferential repair of either adduct under the experimental conditions used. The identification of 15 mutations induced at the hprt locus (of the 44 mutants analysed) showed IQ to be efficient at inducing single base deletions in a run of guanines. Six single guanine deletions were observed in the run of six guanines in exon III and one deletion of a single guanine was observed in a non- repetitive sequence in exon VI. Other mutations observed were two GC-- >TA transversions, two GC-->CG transversions, one AT-->TA transversion and one GC-->AT transition. In addition, two multiple mutations were found. The majority of the identified mutations (12/15) occurred at GC base pairs and suggests either the dG-C8-IQ or the dG-N2-IQ adduct to be the pre-mutagenic lesion.      

Procedures, placement, and risks of further abuse after Munchausen syndrome by proxy, non-accidental poisoning, and non-accidental suffocation

OBJECTIVES: To investigate outcome, management, and prevention in Munchausen syndrome by proxy, non-accidental poisoning, and non-accidental suffocation. DESIGN: Ascertainment through British Paediatric Surveillance Unit and questionnaires to responding paediatricians. SETTING: The UK and Republic of Ireland, September 1992 to August 1994. SUBJECTS: Children under 14 years diagnosed with the above. MAIN OUTCOME MEASURES: Placement and child protection measures for victims and siblings; morbidity and reabuse rates for victims; abuse of siblings; prosecution of perpetrators. RESULTS: Outcome data for 119 with median follow up of 24 months (range 12 to 44 months). No previously diagnosed factitious disease was found to have been caused by genuine disease. Forty six children were allowed home without conditions at follow up. Children who had suffered from suffocation, non-accidental poisoning, direct harm, and those under 5 years were less likely to go home. Twenty seven (24%) children still had symptoms or signs as a result of the abuse at follow up; 108/120 were originally on a child protection register and 35/111 at follow up. Twenty nine per cent (34/118) of the perpetrators had been prosecuted and most convicted; 17% of the milder cases of Munchausen syndrome by proxy allowed home were reabused. Evidence in siblings suggests that in 50% of families with a suffocated child and 40% with non-accidental poisoning there would be further abuse, some fatal. CONCLUSIONS: This type of abuse is severe with high mortality, morbidity, family disruption, reabuse, and harm to siblings. A very cautious approach for child protection with reintroduction to home only if circumstances are especially favourable is advised. Paediatric follow up by an expert in child protection should also occur.     

Sleeping position for infants and cot death in The Netherlands 1985-91

Until the early 1970s the traditional sleeping position for Dutch infants was not prone. After a much publicised lecture in October 1987 on the possible relation between sleeping prone and cot death, the fairly new habit of placing infants prone is being replaced by more traditional positions. The decrease in the prevalence of the prone sleeping position has been documented in six studies. Since 1987 the incidence of registered cot deaths has decreased from 1.04/1000 live births in 1986 to 0.44 in 1991; the real decrease of sudden unexpected death in infancy, however, is greater.     

A survey of basic resuscitation knowledge among resident paediatricians

A telephone questionnaire was undertaken to evaluate the knowledge of resident paediatricians on the subject of the basic resuscitation of the acutely sick child. The questionnaire was targeted at 88 resident paediatricians in hospitals accepting paediatric emergencies in four health regions. Outcome was measured as a correct response to questions based on several emergency scenarios and on the confidence expressed of basic resuscitation knowledge. The subject of emergency management of the child with a compromised upper airway was poorly answered with 40/73 (55%) resident paediatricians suggesting an incorrect endotracheal tube size for an 8 year old child. Fluid management was also deemed unsatisfactory with only 36/73 (49%) providing adequate transfusion secondary to haemorrhagic shock. In addition only 19/73 (26%) mentioned the intraosseous route as a means of obtaining vascular access in a child in extremis. Confidence of the knowledge of basic resuscitation of children was low among resident paediatricians with only 30/73 (41%) expressing confidence and 69/73 (94%) expressing a desire for more formal training in paediatric resuscitation. Resident paediatricians are usually the key personnel in the management of very sick children. This survey demonstrates a low level of basic resuscitation knowledge among resident paediatricians of all grades that must be remedied at a local and national level.     

Psychological response to growth hormone treatment in short normal children

Indian childhood cirrhosis (ICC) is an almost uniformly fatal disease whose outcome may be modified with penicillamine if given at a sufficiently early stage. Twenty nine children with ICC seen in Pune, India, in 1980-7, who had survived at least five years from onset of penicillamine treatment, were reviewed aged 6.3 to 13 years. They were assessed clinically, biochemically, histologically, and by duplex Doppler ultrasound examination. None had symptoms suggestive of liver disease. There were no toxic effects of penicillamine other than asymptomatic proteinuria. Hepatosplenomegaly reduced significantly and liver function tests returned to normal in all. In four children, significant hepatosplenomegaly was associated with an abnormal duplex Doppler hepatic vein flow pattern and micronodular cirrhosis on biopsy. Clinical findings, growth and development, and ultrasound examination were normal in the remainder. Review of serial liver biopsy specimens showed a sequence of recovery from ICC through inactive micronodular cirrhosis to virtually normal histological appearances. The four children who still have micronodular cirrhosis beyond four years from onset remain on penicillamine treatment. In the others penicillamine was stopped after 1-7 (mean 3.5) years without relapse, strong evidence that ICC is not due to an inborn error of copper metabolism.     

Re-evaluating currently available data and suggestions for planning randomised controlled studies regarding the use of hydroxyethyl starch in critically ill patients - a multidisciplinary statement

Introduction

Hydroxyethyl starch (HES) is a commonly used colloid in critically ill patients. However, its safety has been questioned in recent studies and meta-analyses.

Methods

We re-evaluated prospective randomised controlled trials (RCT) from four meta-analyses published in 2013 that compared the effect of HES with crystalloids in critically ill patients, focusing on the adherence to ''presumably correct indication''. Regarding the definition of ''presumably correct indication'', studies were checked for the following six criteria (maximum six points): short time interval from shock to randomisation (<6 h), restricted use for initial volume resuscitation, use of any consistent algorithm for haemodynamic stabilisation, reproducible indicators of hypovolaemia, maximum dose of HES, and exclusion of patients with pre-existing renal failure or renal replacement therapy.

Results

Duration of fluid administration ranged from 90 min up to a maximum of 90 days. Four studies considered follow-up until 90-day mortality, three studies 28-/30-day mortality, whereas four studies reported only early mortality. Included studies showed a large heterogeneity of the indication score ranging between 1 and 4 points with a median (25%; 75% quartile) of 4 (2; 4).

Conclusions

The most important question, whether or not HES may be harmful when it is limited to immediate haemodynamic stabilisation, cannot be answered yet in the absence of any study sufficiently addressing this question. In order to overcome the limitations of most of the previous studies, we now suggest an algorithm emphasising the strict indication of HES. Additionally, we give a list of suggestions that should be adequately considered in any prospective RCT in the field of acute volume resuscitation in critically ill patients.     

Angioplasty and stenting of the superior mesenteric artery in acute mesenteric ischaemia

Acute mesenteric ischaemia is a challenging diagnostic problem with a very high mortality. Traditionally, laparotomy is required for definitive management. We describe a successful case of angioplasty and stenting of the superior mesenteric artery in a surgically unfit patient. We recommend that stenting be considered only in situations where the diagnosis has been made prior to bowel infarction, and if the patient poses a poor operative risk.     

Adjuvant procedures performed during endovascular repair of abdominal aortic aneurysm. does it influence outcome?

OBJECTIVE: The purpose of this study was to assess whether there is a difference in outcome of endovascular repair in patients with and without intraoperative adjuvant procedures. METHODS: Demographic, anatomic and operative details were assessed in patients undergoing endovascular repair using the EUROSTAR registry and correlated with morbidity and mortality rates. Three groups of adjuvant procedures: (A) endovascular, (B) surgical peripheral arterial and (C) surgical abdominal arterial were compared with a group of patients without an adjuvant procedure (D). Logistic regression and Cox proportional hazards model were used for statistical analysis. RESULTS: Of 4631 endovascular repairs, 1353 patients (29.2%) required adjuvant procedures. Additional endovascular procedures were performed in 1057 (78.1%), surgical peripheral arterial in 193 (14.3%) and surgical abdominal arterial in 103 (7.6%). The 30-day mortality rate was significantly higher in categories with peripheral arterial surgical (6.7%) and abdominal surgical procedures (7.8%) compared to patients without adjuvant procedures (1.5%, p = .001 and p = .004, respectively). Life-table-analysis demonstrated that late mortality, conversion or rupture rates were not increased in patients with an adjuvant procedure. CONCLUSION: Adjuvant surgical procedures were associated with increased 30-day mortality. Because of this higher risk, endovascular repair should be recommended with caution when surgical adjuvant procedures are anticipated.