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Biomedical subjects

J Bloch

Publications and source records attributed to J Bloch.

At least 19 recordsLinked to original sources

Parametric oscillation in vertical triple microcavities.

Optical parametric oscillation is a nonlinear process that enables coherent generation of 'signal' and 'idler' waves, shifted in frequency from the pump wave. Efficient parametric conversion is the paradigm for the generation of twin or entangled photons for quantum optics applications such as quantum cryptography, or for the generation of new frequencies in spectral domains not accessible by existing devices. Rapid development in the field of quantum information requires monolithic, alignment-free sources that enable efficient coupling into optical fibres and possibly electrical injection. During the past decade, much effort has been devoted to the development of integrated devices for quantum information and to the realization of all-semiconductor parametric oscillators. Nevertheless, at present optical parametric oscillators typically rely on nonlinear crystals placed into complex external cavities, and pumped by powerful external lasers. Long interaction lengths are typically required and the phase mismatch between the parametric waves propagating at different velocities results in poor parametric conversion efficiencies. Here we report the demonstration of parametric oscillation in a monolithic semiconductor triple microcavity with signal, pump and idler waves propagating along the vertical direction of the nanostructure. Alternatively, signal and idler beams can also be collected at finite angles, allowing the generation of entangled photon pairs. The pump threshold intensity is low enough to envisage the realization of an all-semiconductor electrically pumped micro-parametric oscillator.

Journal Article↗

Electrophysiological characteristics of limbic and motor globus pallidus internus (GPI) neurons in two cases of Lesch-Nyhan syndrome.

OBJECTIVE: Lesch-Nyhan syndrome is a rare and debilitating condition characterized by dystonia and self-mutilating behavior. In order to shed light on the pathophysiology of dystonia, we report the pallidal electrophysiological activity recorded in two patients during deep brain stimulation surgery (DBS). METHODS: Microrecordings were performed on 162 neurons along four tracks aimed at the right and left anterior (limbic) and posterior (motor) globus pallidus internus (GPI). RESULTS: Regardless of the anesthetic agent used (propofol or sevoflurane), both patients showed similar neurons firing rates in the four regions studied, namely the limbic and motor portions of the globus pallidus externus (GPE) or GPI. In both patients, firing rates were similar in the GPE (12.2+/-1.8 Hz, N=38) and GPI (13.2+/-1.0 Hz, N=83) portions of the limbic track, while the motor GPE fired at a higher frequency (23.8+/-2.7 Hz, N=18) than the motor GPI (12.5+/-1.4 Hz, N=23). CONCLUSIONS: These results demonstrate that light propofol or sevoflurane anesthesia influences pallidal activity in a similar way. Electrophysiological recordings suggest that Lesch-Nyhan syndrome might be characterized by analogous firing frequencies in the limbic GPE and GPI while motor GPE would tend to fire at higher rate than the motor GPI. It is therefore tempting to suggest that the symptoms that are observed in Lesch-Nyhan syndrome might result from motor GPI inhibition. SIGNIFICANCE: This observation may confirm the Albin and Delong's model of the basal nuclei in hypokinetic and hyperkinetic disorders.

Child↗

[Skin signs associated with epidermal growth factor inhibitors].

BACKGROUND: Inhibitors of epidermal growth factor receptors (EGFR) constitute a new alternative treatment for patients presenting certain advanced stage solid cancers (bowel, breast, ovary). Adverse cutaneous effects of these drugs are now starting to be described. OBSERVATIONS: Our study involved 2 men and 2 women with no previous history of acne included in a treatment protocol comprising EGFR inhibitors. Mean age was 52 years. The primary cancers were breast, ovary, bowel and unidentified. The EGFR inhibitors used were gefitinib (ZD1839) (2 cases), carnetinib (Cl1033) and cetuximab (IMC-C225). Skin lesions appeared after 7 days and included erythematous papules and follicular pustules of the face, back and upper chest. No comedons were seen, and there were no nodules or cysts. The severity of the rash resulted in discontinuation of treatment in 2 patients with complete disappearance of skin lesions in both cases. In one patient, reduction of the dosage of gefitinib (IMC-C225) led to gradual resolution of the rash. Histological examination of papules and pustules concluded on an acute suppurative folliculitis. Smears and cultures ofa nasal lesion and pustules revealed coagulase-positive Staphylococcus aureus in 2 patients. Combined doxycycline 100 mg daily and benzoyl peroxide was prescribed for 3 months and a favourable outcome was achieved after a mean 2 weeks. DISCUSSION: EGFR inhibitors act by inhibiting mechanisms oftumour proliferation in certain cancers at advanced stages or refractory to other treatments. Our findings in these four patients are similar to the published cases in terms of rapid onset of monomorphous, papulopustular, follicular eruption without comedons. Rapid response to cyclines and benzoyl peroxide is also reported in literature. This treatment must be instituted rapidly and patients must be informed about the cutaneous side-effects of EGFR inhibitors before the start of therapy. The pathophysiology of these eruptions is still unknown. Skin signs are probably due to interaction with EGFR functions, including overexpression of EGFR in keratinocytes and hair follicles.

Adult↗

A study from the EORTC new drug development group: open label phase II study of sabarubicin (MEN-10755) in patients with progressive hormone refractory prostate cancer.

Sabarubicin (MEN-10755), a new synthetic anthracycline analogue, was evaluated for safety and efficacy in a multicentre phase II study in patients with advanced hormone refractory prostate cancer (HRPC). Thirty seven patients were included, of which 34 were evaluable for PSA response according to Bubley's criteria. Sabarubicin was administered as a short (30 min) intravenous infusion at a dose of 80 mg/m(2) every 3 weeks. The main toxicity consisted of grade 3/4 neutropenia in 24 patients (64.9%), with grade 3/4 febrile neutropenia occurring in one patient only. Grade 3/4 cardiotoxicity was observed in 4 patients including one ineligible. Other toxicities were mild. Nine patients achieved a PSA response (26.5%), 10 patients had stable disease (29.4%) and 14 patients disease progression (41.2%). One patient (2.9%) had a PSA response that was not confirmed by repeat PSA testing. The objective response rate according to RECIST criteria was 6.7% in 15 patients with measurable disease. The median duration of PSA responses was relatively long 7.1 months (95% CI 4.9-20.7) as was the median time to treatment progression in patients with stable disease. The median overall survival was 18.7 months (95% CI 9.1-N), comparable to results recently observed in taxotere-containing regimens. To confirm and extend these results, further testing of sabarubicin in larger trials is warranted.

Aged↗

Exciton-photon strong-coupling regime for a single quantum dot embedded in a microcavity.

We report on the observation of the strong-coupling regime between the excitonic transition of a single GaAs quantum dot and a discrete optical mode of a microdisk microcavity. Photoluminescence is performed at various temperatures to tune the quantum dot exciton with respect to the optical mode. At resonance, we observe a clear anticrossing behavior, signature of the strong-coupling regime. The vacuum Rabi splitting amounts to 400 microeV and is twice as large as the individual linewidths.

Journal Article↗

The role of posterior fossa decompression in acute cerebellitis.

BACKGROUND: We present two cases of children who were diagnosed with cerebellitis with acute cerebellar swelling. This rare pathology is potentially fatal, and no clear treatment guidelines are described in the literature. DISCUSSION: Considering our experience, we discuss the different therapeutic strategies and propose aggressive surgical measures consisting of external ventricular drainage and posterior fossa decompression in case of failure of early response to medical treatment to limit secondary cerebellar and brainstem lesions.

Acute Disease↗

A unilateral section of the corticospinal tract at cervical level in primate does not lead to measurable cell loss in motor cortex.

The effects of a unilateral interruption of the dorsolateral funiculus at cervical level on the survival of neurons in the motor cortex were investigated in macaque monkeys. The lesion was made on the left side at the transition region between the 7(th) and 8(th) cervical segments, above the motoneurons controlling hand muscles. As a result, the homolateral hand became paretic, although an incomplete recovery of manual dexterity took place during 2 months post-lesion. A quantitative anatomical assessment of pyramidal neurons in layer V was performed in the hindlimb area of the primary motor cortex and in the supplementary motor area (SMA proper). The pyramidal neurons were visualized using the marker SMI-32 and thus included the subpopulation of corticospinal neurons. These quantitative data demonstrated that the vast majority of the axotomized corticospinal (CS) neurons did not degenerate. Rather, their somata shrank, compared to the opposite hemisphere or to intact monkeys. This conclusion is in contrast to some previous studies in monkeys that argued for a substantial degeneration of motor cortex neurons as a result of transection of the corticospinal tract; yet in agreement with others that concluded the survival of most CS neurons. The survival of the majority of CS axotomized neurons is also consistent with the observation of numerous CS axons 1 mm above the cervical hemisection.

Animals↗

Comparison of the efficacy and safety of combinations of metopimazine or ondansetron with methylprednisolone in the prevention of delayed emesis in patients receiving chemotherapy.

BACKGROUND: Delayed emesis following chemotherapy in cancer patients remains an important challenge for treatment and contributes to poor quality of life and treatment compliance. OBJECTIVES: To compare the efficacy and tolerability of associations of metopimazine and ondansetron with methylprednisolone for the prevention of delayed chemotherapy-induced nausea and emesis. METHODS: A randomised, open-label, observational, cross-over design was used to compare two treatment strategies following two consecutive sessions of chemotherapy separated by at least 1 week. Patients were randomised to treatment with sublingual metopimazine (15 mg tid) or ondansetron lyophilisate (8 mg bid) for 5 days. All patients received oral methylprednisolone (48 mg). Patients reported episodes of nausea and emesis in a diary, and completed the Functional Living Index Emesis quality of life questionnaire. Adverse events were also evaluated. RESULTS: Ninety-nine patients were included in the study, 79.5% of whom were women, with a mean age of 52.7 years. Breast cancer was the most common individual cancer and most patients were receiving combinations of cytotoxic drugs. Treatment was successful at preventing delayed emesis in 73.6% of patients during treatment with the metopimazine-methylprednisolone association and 57.5% during the ondansetron-methylprednisolone association. Analysis of discordant pairs revealed a significant benefit in favour of the methopimazine-methylprednisolone association (p = 0.006). No significant difference was observed between treatments for the overall quality of life score. The incidence of gastrointestinal disorders, particularly constipation, was significantly higher during ondansetron-methylprednisolone treatment (p = 0.0112). CONCLUSION: Methopimazine is an effective and well-tolerated alternative to setrons for the treatment of delayed nausea and emesis in patients undergoing chemotherapy.

Adult↗

Phase II study of OSI-211 (liposomal lurtotecan) in patients with metastatic or loco-regional recurrent squamous cell carcinoma of the head and neck. An EORTC New Drug Development Group study.

The purpose of this study was to evaluate the activity and safety of OSI-211, the liposomal form of lurtotecan, in patients ineligible for curative surgery or radiotherapy and with metastatic/locoregional recurrent squamous cell carcinoma of the head and neck (SCCHN) and target lesions either within a previously irradiated field ("within") or outside a previously irradiated field ("outside"). OSI-211 was given intravenously over 30 min on days 1 and 8 at 2.4 mg/m2/day, repeated every 21 days (1 cycle). From July 2001 to March 2002, 32 patients from 14 institutions were enrolled in the "within" arm and 18 in the "outside" arm. In the "within" arm, two patients were ineligible because their tumour site was not allowed in the protocol (nasopharynx, skin) and two other patients never started treatment. Of the 46 eligible patients who started treatment, there was one objective response (response rate: 2.2% (95% Confidence Interval (CI): [0-11.5%]). Twelve patients in the "within" arm and 6 in the "outside" arm had stable disease, with a median duration of 18 weeks, 95% CI (12.7-25.7). The median time to progression was 6 weeks (95%CI: [5.9-12.7] weeks). Haematological toxicity was moderate in both arms. The most common haematological toxicity was grade 1-2 anaemia in 79% of patients. Non-haematological toxicity was mild in both arms. The most common grade 3-4 non-haematological toxicity was infection in 8.5% of patients. OSI-211 administered on d1 and d8, every 3 weeks, is well tolerated, but shows only minimal activity in locally advanced/metastatic SCCHN.

Adult↗

Neuroprotective gene therapy for Huntington's disease, using polymer-encapsulated cells engineered to secrete human ciliary neurotrophic factor: results of a phase I study.

Huntington's disease (HD) is a monogenic neurodegenerative disease that affects the efferent neurons of the striatum. The protracted evolution of the pathology over 15 to 20 years, after clinical onset in adulthood, underscores the potential of therapeutic tools that would aim at protecting striatal neurons. Proteins with neuroprotective effects in the adult brain have been identified, among them ciliary neurotrophic factor (CNTF), which protected striatal neurons in animal models of HD. Accordingly, we have carried out a phase I study evaluating the safety of intracerebral administration of this protein in subjects with HD, using a device formed by a semipermeable membrane encapsulating a BHK cell line engineered to synthesize CNTF. Six subjects with stage 1 or 2 HD had one capsule implanted into the right lateral ventricle; the capsule was retrieved and exchanged for a new one every 6 months, over a total period of 2 years. No sign of CNTF-induced toxicity was observed; however, depression occurred in three subjects after removal of the last capsule, which may have correlated with the lack of any future therapeutic option. All retrieved capsules were intact but contained variable numbers of surviving cells, and CNTF release was low in 13 of 24 cases. Improvements in electrophysiological results were observed, and were correlated with capsules releasing the largest amount of CNTF. This phase I study shows the safety, feasibility, and tolerability of this gene therapy procedure. Heterogeneous cell survival, however, stresses the need for improving the technique.

Animals↗

Follow-up of 452 totally implantable vascular devices in cystic fibrosis patients.

The use and complications of totally implantable vascular access devices (TIVADs) were examined during multiple courses of antibiotics in cystic fibrosis (CF) patients. This retrospective study involved 36 CF centres. Risk factors for removal and septicaemia were sought by survival analysis of censored data. Multivariate Cox models were constructed with removal or septicaemia as the event and the characteristics of TIVADs as explanatory variables. TIVADs (n = 452) were implanted in 315 patients. The mean functional time per device was 32 +/- 25 months. Long-term complications occurred with 188 devices (42%); they consisted mainly of occlusion (21%, requiring removal in 77%), infection (9.3%, requiring removal in 851%; septicaemia in 7.3%; rate 0.3 per 1,000 days, Candida in 66%), and vascular thrombosis (4.7%, removal in 58%). Multivariate survival analysis showed that removal, whatever the reason, was associated with polyurethane (versus silicone) and routine use of the device for blood sampling (versus never). No risk factors, including heparin lock, were identified for septicaemia or for removal for obstruction. Totally implantable venous access devices appear to be safe and reliable for long-term intermittent venous access. Although retrospective, this study suggests that the characteristics of the material and blood sampling are risk factors for removal.

Anti-Bacterial Agents↗

Non-obstructive hydrocephalus associated with intracranial schwannomas: hyperproteinorrhachia as an etiopathological factor?

BACKGROUND: This series illustrates the association of communicating hydrocephalus with intracranial non-obstructive schwannomas. This association has commonly been observed, however it has only been reported once previously. Moreover, in all the patients we present, hyperproteinorrhachia was a common denominator. This finding may therefore be the underlying mechanism for hydrocephalus. METHOD AND FINDINGS: Seven patients presenting with intracranial schwannomas along with non-obstructive hydrocephalus and hyperproteinorrhachia are reported. Six had a vestibular schwannoma and presented with a unilateral deafness and various degrees of gait disturbance, urinary incontinence and neuropsychological impairment. Due to their advanced ages, these patients underwent a ventriculo-peritoneal shunt, and their symptoms related to hydrocephalus resolved. One patient that suffered from hemifacial dysesthesia and memory deficits presented with a non-obstructive trigeminal schwannoma. In this case the tumour was removed and the hydrocephalus was consequently reversed, and the CSF protein content normalized. INTERPRETATION: The constant finding of hyperproteinorrhachia in all these patients suggests that a high CSF protein content may be the underlying cause of hydrocephalus through a speculative mechanism of decreased CSF resorption.

Adult↗

[National neonatal screening program for cystic fibrosis: management and organization].

France has decided to add to the national neonatal screening program (Phenylketonuria, Hypothyroidism, Congenital Adrenal Hyperplasia, Sickle cell disease) the screening of cystic fibrosis (CF). The screening of CF will be implemented in all regions of France by the end of 2002 and will cover all newborn (near 800,000/year). Based on the recommendation of the French Screening Foundation, the project has been approved by the Health Ministry and will be financed by the social security. CF neonatal screening is now technically feasible and reliable. The proposed methodology includes: immunoreactive trypsin (IRT) dosage on all newborns at day 3 (by radioimmunology "Cis Bio" or immunofluorescence "Delfia") followed by genotype CFTR analysis if IRT level is above 60 micrograms/L. Screening for 29 mutations is planned. If genotype is negative, control of IRT at day 21 will be obtained. Several requirements are included in the program: a protocol of care for the newly diagnosed CF in a specialised CF center; information to all parents of newborns; results of CFTR genotype has to be given during a clinical visit, even if negative. This screening program should allow to screen 98% of the cystic fibrosis patients before the age of 1 month. In order to ensure perfect efficacy, the CF screening program will be evaluated and modified if necessary.

Cystic Fibrosis↗

Brain stem and cerebellar dysfunction after lumbar spinal fluid drainage: case report.

Lumbar spinal fluid drainage is a common procedure to reduce the risks of cerebrospinal fluid (CSF) fistula after skull base fractures or various transdural neurosurgical procedures. Nevertheless, this simple and effective technique can lead to overdrainage and CSF hypovolaemia. This report describes the case of a young patient who had a lumbar drain inserted, to avoid CSF fistula after a pterional craniotomy with opening of the frontal sinus for the clipping of a ruptured aneurysm. The drain was removed after 48 hours because of underdrainage (<1 ml/h). Three days after drain removal, she developed rapid deterioration of her level of consciousness and signs of cranial nerves involvement, brain stem and cerebellar dysfunction. Intracranial pressure was low (<5 cm H(2)O) and MRI showed brain sagging and cerebellar foramen magnum herniation. The patient was successfully treated with epidural blood patch, ventricular drainage, and Trendelenburg position. The authors report this case because CSF hypovolaemia attributable to lumbar overdrainage is an insidious and threatening condition not easy to diagnose in the absence of detectable CSF leak. MRI and intracranial pressure monitoring confirm the diagnosis and permit better understanding of the physiopathology of brain sagging.

Adult↗