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Biomedical subjects

B Wynne

Publications and source records attributed to B Wynne.

14 recordsLinked to original sources

Bacteriologic findings associated with chronic bacterial maxillary sinusitis in adults.

An open-label, multicenter study was performed to assess bacteriologic findings associated with chronic bacterial maxillary sinusitis in adults. Seventy aerobic (52.2%) and 64 anaerobic (47.8%) pathogens were recovered from clinically evaluable patients at baseline (before therapy). The most commonly isolated anaerobes were Prevotella species (31.1%), anaerobic streptococci (21.9%), and Fusobacterium species (15.6%). The aerobes most frequently recovered included Streptococcus species (21.4%), Haemophilus influenzae (15.7%), Pseudomonas aeruginosa (15.7%), and Staphylococcus aureus and Moraxella catarrhalis (10.0% each). Recurrences of signs or symptoms of bacterial maxillary sinusitis associated with anaerobes were twice as frequent as were those associated with aerobes when counts of anaerobes were > or =10(3) cfu/mL. A pathogenic role for Granulicatella species in cases of chronic sinusitis was documented for the first time.

Adult↗

A randomized, placebo-controlled study of rifabutin added to a regimen of clarithromycin and ethambutol for treatment of disseminated infection with Mycobacterium avium complex.

Current guidelines suggest that disseminated Mycobacterium avium complex (MAC) infection be treated with a macrolide plus ethambutol or rifabutin or both. From 1993 to 1996, 198 AIDS patients with MAC bacteremia participated in a prospective, placebo-controlled trial of clarithromycin (500 mg b.i.d.) plus ethambutol (1,200 mg/d), with or without rifabutin (300 mg/d). At 16 weeks, 63% of patients in the rifabutin group and 61% in the placebo group (P = .81) had responded bacteriologically. Changes in clinical symptoms and time to survival were similar in both groups. Development of clarithromycin resistance during therapy was similar in the two groups; of patients who had a bacteriologic response, however, only 1 of 44 (2%) receiving rifabutin developed clarithromycin resistance, vs. 6 of 42 (14%) in the placebo group (P = .055). Thus, rifabutin had no impact on bacteriologic response or survival but may protect against development of clarithromycin resistance in those who respond to therapy.

AIDS-Related Opportunistic Infections↗

Somatostatin and substance P-like immunoreactivity in the auditory brainstem of the adult rat.

The superior olivary complex (SOC) of the adult rat brainstem was studied in detail with regard to its innervation by neural elements showing immunoreactivity for two neuroactive peptides, somatostatin and substance P. Nerve fibres and varicosities showing positive immuno-reactivity for both peptides were particularly dense immediately dorsal and lateral to the lateral superior olivary nucleus (LSO) and dorsal to the superior paraolivary nucleus (SPN). Penetration of this curtain-like innervation into the SPN was limited, and the LSO showed only a very minor innervation by somatostatin-positive structures in its most medial (high frequency) lobe. Dense fibre labelling and varicosities were also apparent for both peptides immediately medial to the ventral and dorsal nuclei of the lateral lemniscus, and in the external cortex and dorsomedial zones of the inferior colliculus (IC). Labelled fibres and endings were also seen in the granule cell regions of anteroventral cochlear nucleus (AVCN) and the most dorsomedial parts of the dorsal cochlear nucleus (DCN). The majority of cells in the medial nucleus of the trapezoid body (MNTB) showed a prominent innervation by nerve terminals that stained positive for somatostatin only whereas the medial superior olivary nucleus (MSO) was devoid of label for both peptides. The ventral nucleus of the trapezoid body (VNTB) showed sparse but significant innervation by both somatostatin and substance P-positive structures. Hence the VNTB was the only defined nucleus of the SOC to show a significant substance P-positive innervation. Neuronal somata immuno-reactive for somatostatin were found in anteroventral and posteroventral cochlear nuclei (AVCN and PVCN) and the A5 and A7 cell groups adjacent to the LSO and the VNLL and DNLL and in all subdivisions of the inferior colliculus (IC). Somata showing only faint immunoreactivity for substance P were found in the VNLL, AVCN and PVCN. These results suggest a potential role for both peptides in auditory signal processing in the adult rat brain.

Age Factors↗

Dopaminergic innervation of the telencephalon of the pigeon (Columba livia): a study with antibodies against tyrosine hydroxylase and dopamine.

The dopaminergic structures in the telencephalon of the pigeon were investigated with antisera against glutaraldehyde-conjugated dopamine (DA) and tyrosine hydroxylase (TH). Our goal was to describe the morphological patterns of the labelled axons and to provide a detailed map of the density and regional distribution of the dopaminergic innervation in relation to cytoarchitectonic areas. DA- and TH-like fibers reached their highest density in the paleostriatum augmentatum and the lobus parolfactorius of the basal ganglia. The paleostriatum primitivum was characterized by a dichotomous DA-positive innervation with a diffuse fiber network contacting enpassant granular cells and a more specific input that completely wrapped up large cells, which probably represent relay neurons. Two distinct DA-positive pathways could be followed back from the forebrain leading to the dopaminergic cell groups of the nucleus tegmenti pedunuculopontinus pars lateralis and the area ventralis tegmentalis. The primary sensory areas of the visual, auditory, somatosensory, and trigeminal systems within the forebrain of the pigeon were virtually devoid of DA-like fibers and demonstrated only TH-positive axons, probably of a noradrenergic nature. Among the limbic structures, the neostriatum caudolaterale (a possible equivalent of the mammalian prefrontal cortex), the septum, the nucleus accumbens, and parts of the archistriatum were heavily labelled by DA-like axons. A highly characteristic morphological feature of the catecholaminergic innervation was the presence of "baskets," which are constituted by TH- and DA-positive fibers coiled up around large perikarya, so that the surrounded somata were virtually visible by the presence of labelled axons. The density of basket and nonbasket type innervations seemed to be independently regulated, so that each forebrain structure could be characterized by a mixture consisting of the individual degrees of these two features. Our results demonstrate that the dopaminergic innervation of the forebrain of the pigeon is widespread but shows important regional variations. Similar to mammals, associative and motor structures are heavily innervated by dopaminergic fibers, whereas sensory areas are dominated by their noradrenergic input. The basket and nonbasket type innervations observed in virtually all of these subdivisions of the telencephalon may indicate the presence of two main classes of catecholaminergic afferents with different mechanisms of modulation of forebrain activity patterns.

Animals↗

Sensitization to apomorphine in pigeons: unaffected by latent inhibition but still due to classical conditioning.

When administered apomorphine, pigeons exhibit protracted bouts of pecking behavior. This response is subject to sensitization, as it initially increases with repeated drug injections. The hypothesis is examined that the sensitization is due to a Pavlovian conditioning of the drug-induced pecking to the environment in which it first takes effect. In a first experiment, we attempted to suppress this conditioning by extensively pre-exposing the birds to the test environment and saline injections (latent inhibition procedure). As the experiment yielded undiminished sensitization, it cast doubt on the conditioning hypothesis. However, while inhibitory pretraining also proved ineffective in a second experiment, a shortening of response latencies specific to the environment in which the animals had first experienced the apomorphine effect supported the conditioning hypothesis. It is suggested that the absence of latent inhibition may be due to the interference of a context-dependent conditioning effect. A third experiment that examined the hypothesis that the reinforcing properties of apomorphine might be attributable to its well known anorectic properties. The results provided some support for this notion. At the same time, they also confirmed that apomorphine-induced pecking conditions reliably to environmental cues. These cues are then by themselves capable of provoking conditioned pecking.

Animals↗

Neurotransmitter and neuromodulator systems of the rat inferior colliculus and auditory brainstem studied by in situ hybridization.

This study was concerned with the distribution of a variety of putative neuromodulator and neurotransmitter systems in auditory regions of the rat brainstem using in situ hybridization histochemistry. Serial brain sections were screened for the presence of mRNAs for (i) precursors of the neuroactive substances cholecystokinin, somatostatin, proenkephalin and substance P (preprotachykinin), (ii) glutamic acid decarboxylase, the key synthesizing enzyme for GABA, or (iii) subunits alpha 1, alpha 2 and alpha 3 of the GABAA receptor. Detectable message for all of these probes was found in at least one auditory brainstem area. There were clear differences in the distribution of the various mRNAs in subregions of the inferior colliculus, superior olivary complex, lateral lemniscus and cochlear nucleus. Cells expressing mRNA for glutamic acid decarboxylase were most prominent in the inferior colliculus, but were also present in all lower auditory brainstem nuclei, except the medial superior olivary nucleus and medial nucleus of trapezoid body. The mRNA for GABAA alpha 1 receptor subunits was detectable in all auditory regions investigated, although at different levels of expression. GABAA alpha 2 and alpha 3 mRNA signals were seen in inferior colliculus, lateral lemniscus and in almost all superior olivary complex regions, but in fewer cells and at lower levels than the GABAA alpha 1 subtype. Moderate to high levels of preprocholecystokinin mRNA expression were seen in all subregions of the inferior colliculus. In other auditory brainstem areas, preprocholecystokinin mRNA levels were either low or absent. With regard to mRNAs for the neuroactive peptides somatostatin, preprotachykinin and preproenkephalin, all were expressed in the inferior colliculus but there were differences in their cellular distribution. For example, there were almost no preprotachykinin mRNA expressing cells in the central nucleus of inferior colliculus and levels of somatostatin mRNA were especially high in the dorsal cortex and in layer 3 of the external cortex of inferior colliculus. There were also differences in the pattern of expression of these mRNAs in the various brainstem auditory nuclei; there was no preprotachykinin mRNA in any part of the superior olivary complex, only somatostatin mRNA was found in the ventral cochlear nucleus, and expression of preproenkephalin mRNA was pronounced in the ventral nucleus of the trapezoid body and the rostral periolivary zone. The data are considered in light of the connectivity and functional organization of the auditory brainstem.

Animals↗

Cefsulodin kinetics in healthy subjects after intramuscular and intravenous injection.

We evaluated cefsulodin kinetics in normal subjects after 250-, 500-, and 1,000-mg, intramuscular injections and 500-, 1,000-, and 2,000-mg 30-min intravenous infusions. Twelve plasma and four urine samples were collected in the first 12 and 24 hr. Plasma samples were analyzed by a new, highly precise high-performance liquid chromatographic procedure developed in our laboratory and urine samples were analyzed microbiologically, using Pseudomonas aeruginosa as the test organism. Mean calculated peak plasma levels from the 250-, 500-, and 1,000-mg intramuscular doses were 5.46, 11.81, and 19.40 microgram/ml. After 500-, 1,000-, and 2,000-mg intravenous infusions peak levels were 32.7, 65.7, and 190.1 microgram/ml. Data from the intramuscular doses were fitted to a one-compartment open kinetic model, yielding a mean elimination half-life (t1/2) of 1.9 hr. Data from the intravenous infusions were fitted to a two-compartment open model, with a mean beta-phase t1/2 of 1.6 hr. Mean 0- to 24-hr urinary recoveries after the three intramuscular doses were 50.0%, 54.5%, and 51.2% of total dose; after the three intravenous doses they were 60.4%, 52.4%, and 54.0%. Cefsulodin kinetics were shown to be consistent and orderly.

Adult↗

Trichosporon cutaneum endocarditis.

A 61-year-old man with Trichosporon cutaneum (T. cutaneum) prosthetic valve endocarditis is reported. He had had an aortic valve replacement for rheumatic heart disease 3 years earlier. Onset of the valve infection was subacute. A systolic murmur was noted on admission. Subsequently, he developed conjunctival hemorrhages, hematuria and transient episodes of confusion, aphasia and cranial nerve palsies. Three of 17 blood cultures taken over 3 weeks were positive for T. cutaneum. He was given amphotericin B (AmB) and 5-fluorocytosine (5FC); T. cutaneum infection of prosthetic aortic valve was identified. The aortic valve was replaced. Postoperatively he developed refractory ventricular fibrillation and died. Striking synergy to AmB-5FC and AmB-rifampin combinations was demonstrated in vitro.

Amphotericin B↗

Frontal forebrain lesions: effects on the foraging and apomorphine pecking of pigeons.

The role of the nucleus basalis prosencephali (Bas), a frontal forebrain structure peculiar to birds, in the control of forage pecking and apomorphine-induced pecking was investigated. In a quasi-natural grit-grain selection task bilateral coagulations of the Bas and the associated neostratum frontolaterale (Nfl) caused a marked fall in grain per peck uptake and a simultaneous increase in grit per peck uptake. Bas lesions also had a reducing effect on the compulsive pecking elicited by systemic injections of apomorphine. This confirms that the Bas is involved in the control of forage pecking and dopaminergic pecking of birds.

Animals↗

Localization of dopamine-beta-hydroxylase-like immunoreactivity in the superior olivary complex of the rat.

The noradrenergic (NA) innervation of the superior olivary complex (SOC) was investigated using a monoclonal antibody against dopamine-beta-hydroxylase (D beta H), the synthesizing enzyme for noradrenaline. In addition, positive labelling of D beta H in the inferior colliculus, the lateral lemniscus (LL) and the cochlear nucleus were documented. The antibody was detected using the highly specific and sensitive ABC immunocytochemical method. The specific aim of the study was to show the distribution of putative NA cells and fibres in the SOC in greater detail than had been previously reported. All investigated auditory regions contained D beta H-positive fibres in varying densities. All superior olivary and periolivary nuclei showed NA innervation by mainly fine, weakly staining fibres. Both nuclei of the LL were also found to contain D beta H-positive fibres. D beta H-positive cell bodies were found in the region of the ventral lateral lemniscus and immediately lateral and dorsal to the lateral superior olivary nucleus. Thus the NA innervation of the superior olivary complex could originate from these regions and/or the locus coeruleus.

Animals↗