Discontinuation of maintenance therapy for cytomegalovirus retinitis in HIV-infected patients receiving highly active antiretroviral therapy.

OBJECTIVE: To study the safety of discontinuing cytomegalovirus (CMV) maintenance therapy among patients with cured CMV retinitis receiving highly active antiretroviral therapy (HAART). METHODS: Patients with a history of CMV retinitis who were receiving anti-CMV maintenance therapy and who had a CD4 cell count > 75 x 10(6) cells/l and a plasma HIV RNA level < 30000 copies/ml while on HAART were included in a multicentre prospective study. Maintenance therapy for CMV retinitis was discontinued at enrolment and all the patients were monitored for 48 weeks by ophthalmological examinations and by determination of CMV markers, CD4 cell counts and plasma HIV RNA levels. T helper-1 anti-CMV responses were assessed in a subgroup of patients. The primary study endpoint was recurrence of CMV disease. RESULTS: At entry, the 48 assessable patients had been taking HAART for a median of 18 months. The median CD4 cell count was 239 x 10(6) cells/l and the median HIV RNA load was 213 copies/ml. Over the 48 weeks, 2 of the 48 patients had a recurrence of CMV disease. The cumulative probability of CMV retinitis relapse was 2.2% at week 48 (95% confidence interval, 0.4-11.3) and that of all forms of CMV disease 4.2%. CMV blood markers remained negative throughout follow-up. The proportion of patients with CMV-specific CD4 T cell reactivity was 46% at baseline and 64% at week 48. CONCLUSIONS: CMV retinitis maintenance therapy may be safely discontinued in patients with CD4 cell counts above 75 x 10(6) cells/l who have been taking HAART for at least 18 months.

Plasma cytomegalovirus DNA, pp65 antigenaemia and a low CD4 cell count remain risk factors for cytomegalovirus disease in patients receiving highly active antiretroviral therapy.

OBJECTIVE: To study the natural history and the current risk factors for cytomegalovirus (CMV) disease in the context of highly active antiretroviral therapy (HAART). SETTING: Prospective multicentre cohort in 15 university hospitals in France. METHODS: A group of 198 patients with CD4 cell count < 100 x 10(6) cells/l (or < 200 x 10(6) cells/l under HAART for at least 2 months), no previous CMV disease and CMV-positive serology were followed every 4 months clinically and for virological testing including HIV RNA and CMV blood markers (culture, pp65 antigenaemia, plasma CMV DNA and CMV late mRNA by the polymerase chain reaction). RESULTS: At inclusion, median CD4 was 77 x 10(6) cells/l (0-308) and 85% of the patients received protease inhibitors. The percentage of patients receiving HAART reached 99% at 12 months. After a follow-up of 23.6 months, the incidence of CMV disease was 3.2/100 patient-years [95% confidence interval (CI) 1.3-5.0]. In univariate Cox models, all the CMV markers, a CD4 cell count remaining < 75 x 10(6) cells/l and an HIV viral load > 100,000 copies/ml were predictive for CMV disease. The hazard ratios for CMV disease were 11 for blood culture; 14 and 70 for pp65 antigenaemia of > or = 1 and > or = 100 nuclei/200,000 cells, respectively; 35 for plasma CMV DNA; 6 for CMV mRNA; 29 for CD4 < 75 x 10(6) cells/l; and 12 for HIV RNA > 100,000 copies/ml. In a stepwise multivariate analysis, only three covariates were independently associated with the occurrence of a disease: plasma CMV DNA, pp65 antigenaemia > or = 100 nuclei/200,000 cells and a CD4 count < 75 x 10(6) cells/l. CONCLUSION: CMV blood markers and CD4 count < 75 x 10(6) cells/l remain risk factors for CMV disease in patients receiving HAART. Analysis of plasma CMV DNA by the polymerase chain reaction is a reproducible and standardized tool that could be used as a decision marker for initiating CMV pre-emptive therapy.

Direct infection of CD34+ progenitor cells by human cytomegalovirus: evidence for inhibition of hematopoiesis and viral replication.

We successfully infected fluorescence-activated cell-sorted CD34+ cells from normal cord blood by the human cytomegalovirus (HCMV) laboratory strain Towne. An inhibitory effect of HCMV on clonogenic myeloid progenitors was observed in primary methylcellulose cultures. After an initial 7-day liquid culture of CD34(+)-infected cells, this inhibition was further amplified in secondary methylcellulose cultures, then involving both the myeloid and erythroid lineages. Under these conditions, viral DNA was detected both in erythroid and myeloid colonies using the polymerase chain reaction (PCR), but reverse transcription PCR (RT-PCR) failed to detect viral RNA. In contrast, when CD34(+)-infected cells were maintained in liquid suspension, both immediate, early, and late transcripts were detected as soon as day 3. In addition, viral production was demonstrated in the culture supernatants, thus confirming that a complete viral cycle occurred under liquid conditions. Furthermore, by resorting cells into CD34+ and CD34- fractions, we showed by RT-PCR that viral replication took place in cells still expressing CD34 antigen, whereas no RNA was found in more differentiated cells that had subsequently lost their CD34 antigen. These findings suggest that HCMV replication can occur at the early steps of progenitor differentiation and may be involved in the viral-induced myelosuppression.

[Esthetic rhinoplasty in the elderly]. / Rhinoplastie esthétique et troisième âge.

The classical refusal to perform rhinoplasty in elderly subjects needs to be revised. In fact, this operation gives satisfactory results provided the patients are well selected on the basis of psychological and anatomical criteria. Apart from the repair of accidental or surgical skin defects, the delayed request from rhinoplasty candidates should be carefully assessed and, when in doubt, the patient may require psychiatric consultation. The major technical problem is that of the lack of elasticity of the skin requiring very moderate modifications of the osteocartilaginous skeleton in every case and occasionally skin resections to allow skin cover of the revised structures. Various techniques for the root of the nose have been proposed. The classical difficulty for elderly people to assume their new body image is more theoretical than real provided "minimal" rhinoplasties are performed. This operation warrants a place in the surgery of ageing.

[For or against rhinoplasty in children?]. / Pour ou contre la rhinoplastie chez l'enfant?

The correction of nasal malformations in children divides surgeons into two groups: those who prefer to operate in order to rapidly restore the altered anatomical structures, and those who prefer to wait and see, to avoid aggravating the initial lesions by operating during the growth period. Clinical findings and animal experiments fail to clearly support either one of these approaches, at least in the case of very young children, but as recent embryological studies have demonstrated the important role of the septum in the growth of the nose, it still seems legitimate to recommend great caution before performing rhinoplasty in children: caution concerning the indications which should take into account major functional problems, caution in deciding the time of operation, which can frequently be delayed, caution in the technique which should be ultraconservative with preservation of the mucoperichondrium, reposition of the displaced fragments and reinclusion in the case of resection, caution in the desired goal of the operation as it is better to obtain a partial result with the possibility of subsequent revision rather than risk serious problems of growth. Rhinoplasty in young children is always difficult and should therefore remain an exceptional procedure.

[Rhinoplasty in the elderly]. / Rhinoplastie chez le sujet âgé.

Though psychological and anatomical conditions are less suitable, cosmetic rhinoplasty in the elderly patient is possible when indicated in selected patients. Their motivations should be looked for. The ones that have been delayed for other reasons are most convenient. The nasal deformities have nothing in particular. Decreased skin elasticity due to ageing is the point to be considered. When this change is moderate, usual surgical technics can be used for mild corrections. Otherwise, cutaneous resections should be limited to the root of the nose in order to carry out an elevation of the skin and a nasal lift. When it's conducted with care, rhinoplasty in the elderly patient deserves its rank in palliative treatment of ageing.

[A controversial procedure: rhinoplasty in children]. / Une intervention controversée: la rhinoplastie chez l'enfant.

Confronted with nose malformations in children, surgeons experience at the same time a legitimate desire to rapidly attend to the altered anatomical structures, and a fear to aggravate the lesions existing initially by operating during a period of growth. Numerous animal experiments have not been conclusive as far as these two contradictory theses are concerned. In all cases, prudence remains mandatory, that is prudence towards the operational indications (important functional impairment), the date of the intervention (risk minimization with age), assessment of expected results (secondary malformations occurring even very late postoperatively).

[Complications and failures of otoplasty]. / Complications et échecs des otoplasties.

Hematoma and infection are particularly serious true complications of otoplasty because of the fragile nature of the cartilage. Perichondritis and chondritis are happily extremely rare sequelae as they may provoke veritable disasters. In contrast, imperfect results due to poor evaluation of protrusion factors or an unadapted technique are encountered less rarely. Schematically they can be divided into anomalies of the external ear in relation to the skull and morphological alterations. The former include overcorrections, or more usually insufficient corrections which may be uni or bilateral, global, or sectorial, particularly affecting the lobe. Among the latter are found poor reconstructions of the anthelix, which constitutes one of the most important elevations on the external ear, but also of the concha or helix. Corrective treatment consists mainly of procedures that were omitted or poorly performed during initial operations. Repeat surgery is always a delicate procedure, and the comments in this report should contribute to avoiding its necessity in the majority of cases.

[Rare tumor of the cavum (mycosis fungoides)]. / Une tumeur rare du cavum (mycosis fongoïde).

A case of mycosis fungoides initiating in the cavum is reported. Results of biopsy of specimens taken from this region were negative, and diagnosis was established only after the appearance of lymph node and cutaneous lesions. The etiology is discussed, particularly in relation to the possible viral nature of the acquired immunodeficiency sundromes and more especially the "gay syndrome".

[Riedel's thyroiditis. Apropos of a case with acute massive fibrous development]. / La thyroidite de riedel. A propos d'un cas d'évolution fibreuse aiguë massive.

Before a brief historical review of the disease, including its classical diagnostic criteria, the authors present a true case of Riedel's thyroiditis. After an initial operation involving virtually complete excision of the affected lobe, the course was particularly rapid with very extensive cervical fibrosis which resulted in death from tracheal and oesophageal complications. Such rapidly progressive secondary fibrosis has not been described before and did not have the histological characteristics of a recurrence. The authors liken it to phenomena of fibrosis frequently described as being associated with Riedel's disease (retroperitoneal fibrosis, fibrosing cholangitis, orbital pseudotumour, etc.). Bearing in mind that glucocorticosteroids have a beneficial action on such sites, the authors wonder whether routine preoperative corticosteroid therapy might not have avoided such an early fatal outcome in this patient.

[Injuries of the nose in the newborn and young infant]. / Traumatismes du nez chez le nouveau-né et le jeune enfant.

After having emphasized the frequency of the newborn's and young child's nasal fractures, the authors insist on the difficulty of: - a precise outcome of the lesions, - the complications due to nasal obstruction, - the impossibility to anticipate the evolution of these lesions, which is being precised by a brief embryological recall. The traumas are deliberately presented according to the age of the patients: 1) the newborn's fractures: - the prenatal fractures, which generally have a favorable evolution. - obstetrical traumas, with nasal obstruction and feeding difficulty, both being indications to surgery. 2) The young child's fractures: often misknown, and relatively frequent, the nasal wall's hematoma is a dreadful complication. 3) During school years: (sports, car accidents, Silverman's syndrome) Nasal fractures are here generally associated to other facial lesions. Indications to surgery: Always: If it is a recent fracture, provoquing nasal obstruction with respiratory and feeding problems. Sometimes: Septoplasty as minima in case of respiratory difficulties. Never perform true rhinoplasty and/or osteotomies.

[Palliative surgery for facial paralysis]. / La place de la chirurgie palliative dans le traitement des paralysies faciales.

Palliative surgery in patients with facial paralysis can be a useful temporary measure before nerve recuperation occurs, or a definitive procedure in cases with permanent loss of the effector muscle. Valid results can be obtained in the periorbital region by performing an external blepharorraphy, together with various static or dynamic procedures for louvering of the upper eyelid. The fascia lata is usually employed to obtain suspension, reequilibrium of soft tissues being ensared by lifting and localized cutaneous resections. Marked hyperactivity on the apposing side can be reduced by selective neurectomies.

[Lethal midline granuloma of unknown cause: 6 new cases and review of the literature]. / Granulome malin centro-facial de cause inconnue: six nouvelles observations et revue de la littérature.

The term of "lethal midline granuloma" has been used to apply to a number of diseases. In this paper, it is argued that this term should be only a clinical description of a relentlessly progressive destructive lesion of the nose and face. A list of all the possible causes is presented. There is a group of patients who do not correspond to any specific etiology. Reviewing the observations in the literature and our own, we think that such cases are best classified according to their histological appearance. Those without atypical cells (20% of cases) are always localized to the upper respiratory tract, while those with atypical cells (histiocytes?), 80% of cases, may become generalized and/or may evolve to a malignant lymphoma. When localized, both forms (with and without atypical cells) respond very well to high-dose radiation therapy (40 to 60 Gy). In disseminated forms or relapses following radiotherapy treatment, chemotherapy, the only available alternative treatment, has met with little success. We present the clinical and pathological features of six such patients, of whom one had no atypical cells. Radiotherapy produced a clinical remission in five of five cases, but of shorter duration than that reported in the literature. No treatment other than radiotherapy has yet proven to be regularly efficient in this rare and mutilating disease.

[Reflections concerning the reconstruction of the pinna of the ear (author's transl)]. / Reflexions sur la reconstruction du pavillon de l'oreille.

Reconstruction of the pinna of the ear is a difficult enterprise and overall results are poor. It is nevertheless essential to persist since despite the hazards of such surgery many patients wish to have an operation since they are unable to tolerate their deformity. Apart from the cutaneous problem, the most important point remains that of bitterness. There are still many partisans of the use of costal cartilage, but it would seem legitimate to also try new implantable substances, in particular microporous. Whatever the choice, it is important in all cases to establish a programme rather then improvise. This is the only way to reduce the number of operative stages, to avoid untoward scars and to decrease the number of "touching up" procedures. Despite the many difficulties which must still be resolved, a certain number of modern studies offer hope of an improvement in results.