[Outcome of women younger than 30 years of age followed for untreated high-grade cervical intraepithelial lesion]. / Devenir des femmes de moins de 30 ans prises en charge pour une lésion intra-épithéliale de haut grade du col utérin non traitée.

OBJECTIVES: To assess the probability of spontaneous regression of high grade cervical intraepithelial neoplasia (HGCIN) in women under 30 and the predictive factors for such evolution. METHODS: We conducted a bicentric retrospective study. A total of 98 patients under 30 and with untreated HGCIN were included from 01/01/2010 to 31/12/2019. For each patient, the initial clinical and colposcopic characteristics were systematically documented. In compliance with French guidelines, these patients were offered repeated 6-months colposcopic follow-up for 2years. The endpoint was the occurrence of spontaneous regression of the HGCIN defined by normalization of colposcopy, and/or a negative biopsy and/or a negative HPV test or histological regression to low grade CIN, or a colposcopy showing simple minor abnormalities requiring no biopsy. RESULTS: Spontaneous HGCIN regression was observed in 37/98 patients. The median follow-up was of 16 (10.5-24.3) months. Predictive factors for spontaneous regression were: minor initial cytological abnormalities (HR=3.4; 95% CI: 1.02-11.05) and grade 1 atypical transformation at initial colposcopy (TAG1) (HR=2.3; 95% CI: 1.1-4.7). CONCLUSION: Before 30, the probability of spontaneous regression of HGCIN exists but remains low. Predictive factors for such evolution are minor initial cytological abnormalities and TAG1 colposcopic impression.

Expression of chemokine and inhibitory receptors on natural killer cells: effect of immune activation and HIV viremia.

We examined the cell-surface expression of chemokine and natural killer (NK) cell inhibitory receptors (iNKRs) on NK cells from individuals with human immunodeficiency virus (HIV) infection, chronic hepatitis C infection, and Wegener's granulomatosis (WG), an inflammatory, granulomatous vasculitis. The expression of CCR5 on NK cells was up-regulated in individuals with HIV viremia and in individuals with active WG, indicating that expression of this receptor is modulated by states of immune activation associated with viral infection and inflammatory or immune-mediated diseases. In contrast, iNKRs were shown to be up-regulated only on NK cells of individuals with HIV viremia, and they returned to a normal level when viremia was controlled with effective antiviral therapy. In individuals with HIV-1 viremia, there was a direct correlation between the level of expression of p58.1, p58.2, and CD94 receptors and plasma HIV viremia, suggesting that ongoing active HIV replication has an effect on the expression of such receptors on NK cells. These results suggest that immune activation leads to abnormal cell-surface expression of chemokine receptors on NK cells, whereas HIV-specific processes account for the up-regulation of iNKRs on NK cells; this may explain the NK cell-functional defects seen in HIV infection.

Hypothesis for generation of the unstable Hb Bucuresti (beta 42 Phe-->Leu) mutation.

INTRODUCTION: Unstable hemoglobin disorders are characterized by a congenital, mostly familial chronic hemolytic anemia with episodes of severe hemolysis during febrile illnesses. Usually, isopropanol and heat stability tests lead to the diagnosis which is confirmed by protein and gene sequencing. Generation of the mutations is still a subject of controversy. PATIENT, MATERIALS AND METHODS: We describe a 6-year-old Swiss child with congenital hemolytic anemia and a negative family history. Hemoglobin was studied by IEF, HPLC reverse phase chromatography, heat stability and isopropranol tests. DNA was sequenced in both coding and non-coding strands. RESULTS: An unstable Hb was diagnosed on the basis of positive heat stability and isopropranol tests. The TTT-->TTG mutation at codon 42 corresponding to a Phe-->Leu substitution was found on DNA sequencing. Paternity was confirmed indicating that we are dealing with a new mutation. CONCLUSION: So far, three different mutations at codon 42 of the beta-chain, and two at the corresponding position of the alpha-chain have been described, all leading to a hemolytic anemia. These mutations can either represent random phenomena occurring at an important location in the heme pocket, or may be secondary to the two highly homologous zones present in this region. These homologous zones may indicate a hot spot for point mutations created by abnormal crossing over or formation of loops, and an imperfect DNA repair process.

Prevalence of the use of herbal products in a low-income population.

OBJECTIVES: This study determined the prevalence of herb/supplement use in a low-income population and determined the providers' level of knowledge about herbs/supplements. METHODS: Adult English-speaking patients seen at a rural family practice residency clinic were offered an anonymous survey. Another survey was developed for the clinic providers. Data were analyzed using the chi-square test. RESULTS: Fifty-six percent of a low-income population use herbs/supplements; 41% of all users cited friends or relatives as their main source of information, and 53% of users had not informed their provider. In the provider survey, 69% of the providers indicated that they had received no education about herbs/supplements, yet 71% were asked about them by patients at least twice a month. CONCLUSIONS: Because herb/supplement use occurs across all demographic groups, all patients should be questioned about their use of such substances. Currently, few providers are prepared to guide their patients about herbs/supplements. Efforts should be made to educate health care providers about common herbs/supplements.

Successful treatment of invasive aspergillosis in chronic granulomatous disease by bone marrow transplantation, granulocyte colony-stimulating factor-mobilized granulocytes, and liposomal amphotericin-B.

X-linked chronic granulomatous disease (X-CGD) is a primary immunodeficiency with complete absence or malfunction of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in the phagocytic cells. Life-threatening infections especially with aspergillus are common despite optimal antimicrobial therapy. Bone marrow transplantation (BMT) is contraindicated during invasive aspergillosis in any disease setting. We report an 8-year-old patient with CGD who underwent HLA-genoidentical BMT during invasive multifocal aspergillus nidulans infection, nonresponsive to treatment with amphotericin-B and gamma-interferon. During the first 10 days post-BMT, the patient received granulocyte colony-stimulating factor (G-CSF)-mobilized, 25 Gy irradiated granulocytes from healthy volunteers plus G-CSF beginning on day 3 to prolong the viability of the transfused granulocytes. This was confirmed in vitro by apoptosis assays and in vivo by finding nitroblue tetrazolium (NBT)-positive granulocytes in peripheral blood 12 and 36 hours after the transfusions. Clinical and biological signs of infection began to disappear on day 7 post-BMT. Positron emission tomography with F18-fluorodeoxyglucose (FDG-PET) and computed tomography (CT) scans at 3 months post-BMT showed complete disappearance of infectious foci. At 2 years post-BMT, the patient is well with full immune reconstitution and no sign of aspergillus infection. Our results show that HLA-identical BMT may be successful during invasive, noncontrollable aspergillus infection, provided that supportive therapy is optimal.

Greater omentum flaps and granulocyte transfusions as combined therapy of liver abscess in chronic granulomatous disease.

We report the case of a 17-year-old boy with gp91phax-deficient chronic granulomatous disease who developed a liver abscess due to Staphylococcus aureus. Despite treatment with appropriate antibiotics and gamma interferon for three months as well as incision and drainage, the abscess persisted unchanged in size. After surgical debridement, the abscess cavity was filled with two pedunculated greater omentum flaps as a direct feeder road of granulocytes to the infectious focus. An average of 48.5 x 10(9) granulocytes a day harvested from G-CSF-prestimulated donors were transfused for a total of 8 days without side effects. Ultrasound 3 months later showed no residual abscess. Combination of greater omentum flaps and transfusion of G-CSF-prestimulated granulocytes may be the optimal treatment for liver abscesses refractory to conventional therapy.

An experimental comparative study on the characteristics of ventricular fibrillation during cardiac arrest and methoxamine administration.

The effect of a pure alpha-adrenergic agent, methoxamine on ventricular fibrillation (VF) amplitude and the relation between hemodynamic parameters and survival in a rodent cardiopulmonary resuscitation (CPR) model were studied. Our results suggested that: 1) VF amplitude decreased during untreated VF, but it increased during pericardial chest compression: 2) methoxamine significantly increased the mean aortic pressure (MAP) and coronary perfusion pressure (CPP) but not VF amplitude, and the survival also increased due to elevation of CPP; and 3) all surviving animals with successful defibrillation had a higher VF amplitude.

Effect of different drugs on end-tidal carbon dioxide during rodent CPR.

The purpose of this study was to investigate the effect of non-adrenergic agents on cardiopulmonary resuscitation (CPR) and end-tidal CO2 (ETCO2) during CPR in a rodent model. Our results suggested that: 1) coronary perfusion pressure (CPP) after drugs infusion was increased significantly by methoxamine, arginine vasopresin (AVP) and angiotension-II (ANG-II), but not by endothelin-1 (ET-1); 2) ETCO2 prior to defibrillation was decreased significantly by a pure alpha 1 adrenergic agents, methoxamine and were increased significantly by non-adrenergic agents, ANG-II and ET-1 during rodent CPR; 3) a significant positive correlation between ETCO2 and CPP was observed in AVP group, suggesting that AVP have little effect on pulmonary circulation; and 4) methoxamine, AVP and ANG-II have similar effect on resuscitability during rodent CPR.

Future directions for resuscitation research. IV. Innovative advanced life support pharmacology.

The topics discussed in this session include a partial review of laboratory and clinical studies examining the effects of adrenergic agonists on restoration of spontaneous circulation after cardiac arrest, the effects of varying doses of epinephrine, and the effects of novel vasopressors, buffer agents (NaHCO3, THAM, 'Carbicarb') and anti-arrhythmics (lidocaine, bretylium, amiodarone) in refractory ventricular fibrillation. Novel therapeutic approaches include titrating electric countershocks against electrocardiographic power spectra and of preceding the first countershocks with single or multiple drug treatments. These approaches need to be investigated further in controlled animal and patient studies. Epidemiologic data from randomized clinical outcome studies can give clues, but cannot document pharmacologic mechanisms in the dynamically changing events during attempts to achieve restoration of spontaneous circulation from prolonged cardiac arrest. Also, rapid drug administration by the intraosseous route was compared with intratracheal and intravenous (i.v.) drug administration. Many studies on the above treatments have yielded conflicting results because of differences between healthy hearts of animals and sick hearts of patients, differences in arrest (no-flow) times and cardiopulmonary resuscitation (CPR) (low-flow) times, different pharmacokinetics, different dose/response requirements, and different timing of drug administration during low-flow CPR versus during spontaneous circulation. The need to stabilize normotension and prevent rearrest by titrated novel drug administration, once spontaneous circulation has been restored, requires research. Most of the above topics require some re-evaluation in clinically realistic animal models and in cardiac arrest patients, especially by titration of old and new drug treatments against variables that can be monitored continuously during resuscitation.

Future directions for resuscitation research. III. External cardiopulmonary resuscitation advanced life support.

This discussion about advanced cardiac life support (ACLS) reflects disappointment with the over 50% of out-of-hospital cardiopulmonary resuscitation (CPR) attempts that fail to achieve restoration of spontaneous circulation (ROSC). Hospital discharge rates are equally poor for in-hospital CPR attempts outside special care units. Early bystander CPR and early defibrillation (manual, semi-automatic or automatic) are the most effective methods for achieving ROSC from ventricular fibrillation (VF). Automated external defibrillation (AED), which is effective in the hands of first responders in the out-of-hospital setting, should also be used and evaluated in hospitals, inside and outside of special care units. The first countershock is most important. Biphasic waveforms seem to have advantages over monophasic ones. Tracheal intubation has obvious efficacy when the airway is threatened. Scientific documentation of specific types, doses, and timing of drug treatments (epinephrine, bicarbonate, lidocaine, bretylium) are weak. Clinical trials have failed so far to document anything statistically but a breakthrough effect. Interactions between catecholamines and buffers need further exploration. A major cause of unsuccessful attempts at ROSC is the underlying disease, which present ACLS guidelines do not consider adequately. Early thrombolysis and early coronary revascularization procedures should also be considered for selected victims of sudden cardiac death. Emergency cardiopulmonary bypass (CPB) could be a breakthrough measure, but cannot be initiated rapidly enough in the field due to technical limitations. Open-chest CPR by ambulance physicians deserves further trials. In searches for causes of VF, neurocardiology gives clues for new directions. Fibrillation and defibrillation thresholds are influenced by the peripheral sympathetic and parasympathetic nervous systems and impulses from the frontal cerebral cortex. CPR for cardiac arrest of the mother in advanced pregnancy requires modifications and outcome data. Until more recognizable critical factors for ROSC are identified, titrated sequencing of ACLS measures, based on physiologic rationale and sound judgement, rather than rigid standards, gives the best chance for achieving survival with good cerebral function.

Atypical Kawasaki disease with peripheral gangrene and myocardial infarction: therapeutic implications.

We describe a 2-month-old girl with atypical Kawasaki disease (KD) complicated by peripheral gangrene and myocardial infarction. Peripheral ischaemia leading to gangrene is a rare but serious complication of KD in infants younger than 7 months of age. Treatment has been targeted at reducing arterial inflammation, arteriospasm and thrombosis. We report the first patient with incomplete KD and peripheral ischaemia in whom therapy with prostaglandin E1 (PGE1) as vasodilating and antithrombotic agent appeared successful, restoring hand and foot perfusion without significant long-term sequelae. However, PGE1 could have supported development of myocardial infarction by shunting blood away from ischaemic areas distal to a giant coronary artery aneurysm with beginning thrombosis. CONCLUSION. Atypical KD with peripheral gangrene appears to react favourably to treatment with PGE1, but needs careful monitoring to detect early signs of cardiac ischaemia.

[Prehospital resuscitation in urban conditions--results and prognostic decision criteria]. / Prähospitale Reanimation in städtischen Verhältnissen--Ergebnisse und prognostische Entscheidungskriterien.

From 1983 to 1991, 214 patients (age 62 +/- 15 years; 72% male) with out-of-hospital cardiac arrest were resuscitated in the field and transported to the hospital with basic cardiac life support only (manual chest compression, assisted ventilation by bag-air-valve). In 64 patients (30%; 95% confidence interval [CI]: 24-36%) a stable circulation allowing admission to the intensive care unit was restored in the emergency room. 26 patients (12%; CI: 8-17%) survived to hospital discharge. 20 patients showed no or only mild neurological impairment, 4 had moderate cognitive deficits, and 2 patients were in a permanent vegetative state. Multiple logistic regression revealed bystander resuscitation before arrival of the ambulance (odds ratio [OR]: 4.7 [CI: 1.5-14.7]; p < 0.01) and ventricular fibrillation on arrival in the emergency room (OR: 42.8 [CI: 5.2-350]; p = 0.0005) to be statistically significant predictors of survival. These data justify continuation and extension of resuscitation efforts in the emergency room if patients were given only basic cardiac life support in the field and during transport. Patients who arrive in ventricular fibrillation and who were resuscitated by a bystander prior to the arrival of the ambulance team have a realistic chance of survival. Delegation of competence to defibrillate to trained, non-physician ambulance personnel may reduce the duration of cardiac arrest in patients with ventricular fibrillation and thus save lives.

Survival after failed out-of-hospital resuscitation. Are further therapeutic efforts in the emergency department futile?

BACKGROUND: Because of extremely poor outcomes, the practice of continuing cardiopulmonary resuscitation in hospital emergency departments after unsuccessful out-of-hospital cardiopulmonary resuscitation has been strongly questioned. Before revising our institutional guidelines according to previous pessimistic reports we wished to review our own experience with this practice. METHODS: The case histories of 141 consecutive victims of witnessed cardiac arrest brought to the emergency department with ongoing cardiopulmonary resuscitation were reviewed. The emergency medical system was two-tiered and was based on the emergency department of a single university hospital. The first tier, staffed with emergency medical technicians, provided only basic cardiac life support. The second, physician-staffed tier provided advanced cardiac life support and was allowed to terminate resuscitation in the field. Rates of successful resuscitation, survival to discharge and after 1 year, and the cerebral performance of resuscitated and surviving patients were determined. RESULTS: Ninety-one patients (65%) died in the emergency department; 50 (35%) were resuscitated and admitted. Thirty-two patients (23%) died in the hospital, 18 (13%; 95% confidence interval, 8% to 20%) survived to discharge. Sixteen survivors showed no or only mild neurologic impairment at discharge. Seventeen patients were alive 1 year later. Bystander resuscitation, short intervals to initiation of resuscitation, and ventricular fibrillation at emergency department entry were significantly associated with survival. CONCLUSIONS: Institutional guidelines for the decision whether to continue resuscitation after failed out-of-hospital efforts should be based on an analysis of the characteristics and results of the local emergency medical system. Continuing efforts in the hospital may not be inevitably futile.

ETCO2 monitoring during low flow states: clinical aims and limits.

End-tidal carbon dioxide concentration in the expired air (ETCO2) is measured with different technologies. ETCO2 allows the global evaluation of three main body functions: metabolism, circulation and ventilation. If two of these parameters are held constant, changes in ETCO2 reflect a variation of the third. Thus, ETCO2 is now widely used as a reliable monitoring device in various clinical settings. In the past years several studies proposed ETCO2 as a noninvasive monitor for the evaluation of therapeutic efforts during low-flow states, and especially during cardiopulmonary resuscitation. However, recent laboratory and clinical investigations demonstrated that various pharmacological and physical interventions may influence ETCO2. Especially, the use of the CO2 generating buffer NaHCO3 increase and alpha-adrenergic agents constantly decrease ETCO2. Thus, although ETCO2 remains a necessary tool during anaesthesia, it may loose the potential for prediction of survival when monitoring the resuscitative efforts during cardiopulmonary resuscitation.