Positron emission tomographic investigations of central muscarinic cholinergic receptors with three isomers of [76Br]BrQNP

We studied the potential of three radiobrominated isomers of BrQNP, (Z(-,-)-[⁷⁶Br]BrQNP,E(-,-)-[⁷⁶Br]BrQNP andE(-,+)-[⁷⁶Br]BrQNP), as suitable radioligands for imaging of central muscarinic cholinergic receptors in the human brain. These radioligands were stereospecifically prepared by electrophilic radiobromodestannylation of the respective tributylstannyl precursors using no-carrier-added [⁷⁶Br]BrNH₄ and peracetic acid. Preliminary pharmacological characterizations were determined by biodistribution, autoradiography, competition, displacement and metabolite studies in rats. The (-,-)-configuration presented important specific uptakes in brain muscarinic cholinergic receptor (mAChR)-rich structures and in heart, low metabolization rates and an apparent M₂ selectivity. The (-,+)-configuration revealed more rapid clearance, lower uptake, a higher metabolization rate and an apparent M₁ selectivity. Reversibility of the binding was confirmed for the three radiotracers. Positron emission tomography in the living baboon brain revealed high and rapid uptake in the brain and accumulation in the mAChR-rich structures studied. At 30 min p.i., theE(-,-)-radiotracer reached a plateau in cortex, pons and thalamus with concentrations of 29%, 24% and 19% ID/l, respectively.Z(-,-)-[⁷⁶Br]BrQNP also accumulated in these structures, reaching a maximal uptake (27% ID/l) in the cortex 2 h p.i. At 5 min p.i. a plateau (17% ID/l) was only observed in the cortex for theE(-,+)-[⁷⁶Br]BrQNP; by contrast, the other structures showed slow washout. After 3 weeks, the (-,-)-radiotracers were studied in the same baboon pretreated with dexetimide (1 mg/kg), a well-known muscarinic antagonist. In all the mAChR structures, the highly reduced uptake observed after this preloading step indicates that these radiotracers specifically bind to muscarinic receptors.Z(-,-)-[⁷⁶Br]BrQNP, which is displaced in higher amounts from M₂ mAChR-enriched structures, reveals an M₂ affinity. The two isomers having the (-,-)-configuration are potential probes for investigating central muscarinic receptors. The absolute configuration on the acetate chiral centre influences their muscarinic subtype selectivity and thecis-trans isomerism of the vinyl moiety affects their specific fixation.     

Gadolinium ring enhancement and mass effect in acute disseminated encephalomyelitis

A 9-year-old boy presented with a subacute history of optic neuritis followed by brainstem involvement, with fever and a lymphocytic pleocytosis in the cerebrospinal fluid. Gadolinium-enhancing ring lesions were demonstrate in the white matter of the cerebrum, brainstem and cerebellum on day 17 of the illness, all appearing simultaneously as part of a monophasic illness. A parietal lesion exerted mass effect. Needling and biopsy yielded no evidence of a pyogenic lesion, tumour or tuberculosis and showed vasculitis. There was insufficient material for myelin staining. Dexamethasone therapy lead to rapid improvement of the radiological lesions: MRI and CT on day 34 of the illness showed complete clearing of the lesions except for residual abnormality at the biopsy site.     

Rhinophyma. The value of progressive dermabrasion]

After briefly summing up the nosology of rhinophyma, the authors report their experience with the surgical correction of this nasal disease, on the basis of eight cases. They explain their reasons for giving up dermasection and preferring dermabrasion.     

LEMMA: A Language for Easy Medical Models Analysis

The quality of health care systems and processes is becoming a prominent problem and more and more efforts are devoted to define methodologies and tools to measure and assure quality of care. New methods are required to optimize health care processes to guarantee high quality standards within (limited) available resources. Resource optimizations able to preserve the quality of treatments require good models of medical processes. This paper presents LEMMA, a new notation to model medical processes. LEMMA provides physicians with intuitive graphical elements to design their models. At the same time a high level timed Petri net corresponding to the designed model is built automatically. In this way, LEMMA models are ascribed formal semantics and can be executed and analyzed automatically. The dual language approach followed in this paper allows physicians to gain all the benefits of formal methods without being proficient in them. Medical users manage simple graphical elements, while Petri nets ensure formality and validation capabilities. In this way LEMMA mixes formal and informal notations, overcoming the problems of both the approaches. The definition of the notation has been supported by the development of an environment to design LEMMA models. The environment, besides letting us experiment with the notation, has been employed to define and analyze real case studies.     

Tuberculosis in healthcare workers caring for a congenitally infected infant.

OBJECTIVE: To assess the extent of nosocomial transmission of tuberculosis among infants, family members, and healthcare workers (HCWs) who were exposed to a 29-week-old premature infant with congenital tuberculosis, diagnosed at 102 days of age. DESIGN: A prospective exposure investigation using tuberculin skin test (IST conversion was conducted. Contacts underwent two skin tests 10 to 12 weeks apart. Clinical examination and chest radiographs were performed to rule out disease. Isoniazid prophylaxis was administered to exposed infants at higher risk. SETTING: A neonatal intensive care unit in an urban hospital in Brussels, Belgium. PARTICIPANTS: Ninety-seven infants, 139 HCWs, and 180 visitors. RESULTS: Newly positive TST results occurred in HCWs who had been in close contact with the infant. Six (19%) of 32 primary care nurses and physicians had TST conversions and received treatment. Among the 97 exposed infants, 85 were screened and 34 were identified as at higher risk of infection. Of these, 27 received preventive isoniazid. None of the infants and none of the 93 other infants' family members evaluated were infected. CONCLUSIONS: Congenital tuberculosis in an infant poses a risk for nosocomial transmission to HCWs. Delayed diagnosis of this rare disease and close proximity are the most important factors related to transmission.     

Procedural learning in schizophrenia can reflect the pharmacologic properties of the antipsychotic treatments.

BACKGROUND: Conventional and atypical antipsychotics have different affinities for D2 receptors, and these receptors are principally located in the striatum. Given that this cerebral structure was previously found to play a major role in procedural learning, the antipsychotic treatment in schizophrenia may be determinant for the procedural learning profile of these patients. OBJECTIVE: The current study was aimed at verifying whether procedural learning differs in patients with schizophrenia treated with conventional antipsychotics and patients treated with atypical antipsychotics. METHOD: Forty-five patients with schizophrenia were divided into 3 different groups according to their pharmacologic treatment: (1) haloperidol, a classical neuroleptic with high D2 receptor affinity; (2) clozapine, an atypical neuroleptic with practically no D2 receptor affinity; and (3) risperidone, an atypical neuroleptic that nevertheless shows high D2 receptor affinity. Patients were compared to 35 control subjects on a visuomotor procedural learning task (mirror drawing). RESULTS: All patients were able to learn the task. However, those treated with haloperidol showed some degree of learning impairment, while those treated with clozapine or risperidone did not show this impairment. In addition, performance per se, regardless of the learning, was found to be affected in the haloperidol and risperidone, but not in the clozapine groups. CONCLUSION: Procedural learning in schizophrenia may be differentially affected, depending on the pharmacologic profiles of the antipsychotics used for the treatment of this illness.