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Biomedical subjects

D Wong

Publications and source records attributed to D Wong.

At least 271 records · Page 15Linked to original sources

Clinical pharmacology of tomoxetine, a potential antidepressant.

Tomoxetine (LY139603) selectively inhibits norepinephrine uptake in animals and has activity in animal models of depression. Tomoxetine was administered in single oral doses up to 90 mg to healthy normal volunteers. In addition, normal human subjects received either 20 or 40 mg of tomoxetine b.i.d. for 1 week to evaluate the safety and pharmacologic activity of the compound in humans. At these doses, no serious drug-related adverse effects were encountered. Activity of the compound at the lower dose (20 mg b.i.d.) was evaluated by examining changes in the pressor responses to infused norepinephrine and tyramine and by determining [3H]serotonin uptake in platelets harvested from subjects receiving the compound. Pressor sensitivity to norepinephrine was increased by 261 +/- 69% of control, and pressor sensitivity to tyramine was decreased by 51 +/- 6% of control during treatment. Changes in the pressor sensitivity to norepinephrine in individual subjects were positively correlated with drug levels. There were no statistically significant changes in platelet [3H]serotonin uptake. These results indicate that tomoxetine selectively inhibits norepinephrine uptake in humans at doses which are clinically well tolerated and suggest that tomoxetine has potential clinical use as an antidepressant.

Adult↗

Spatial tuning of auditory neurons in the superior colliculus of the echolocating bat, Myotis lucifugus.

The azimuthal selectivity of auditory neurons was examined in the superior colliculus of the little brown bat, Myotis lucifugus. Frequency-modulated (FM) sounds, synthesized to mimic biosonar signals the echolocating bat naturally hears, were delivered from a loudspeaker moving across the front of the unanesthetized animal. Neurons were classified on the basis of their spatial tuning into two general classes: (i) hemifield units (34%) were broadly tuned to the contralateral side irrespective of sound pressure level; (ii) azimuth-sensitive units (66%) were sharply tuned to different azimuths at sound pressures near their minimum thresholds (MTs). A distinguishing feature of these azimuth-sensitive neurons is that they responded maximally to a sound source located at a preferred azimuth (best azimuth) for levels as high as 30 dB above their MT. Mapping experiments provide evidence of a sequential representation of best azimuth along the rostrocaudal extent of the superior colliculus, with sounds originating from 0-10 degrees ipsilateral coded at the rostral end, and from 30-40 degrees contralateral coded at the caudal end. The highly directional echolocation system of Myotis probably accounts for the limited azimuthal representation of echo-source spanning mainly 40 degrees to either side of its line of flight.

Acoustic Stimulation↗

Frequency and amplitude representations in anterior primary auditory cortex of the mustached bat.

The orientation sound emitted by the Panamanian mustached bat, Pteronotus parnellii rubiginosus, consists of four harmonics. The third harmonic is 6-12 dB weaker than the predominant second harmonic and consists of a long constant-frequency component (CF3) at about 92 kHz and a short frequency-modulated component (FM3) sweeping from about 92 to 74 kHz. Our primary aim is to examine how CF3 and FM3 are represented in a region of the primary auditory cortex anterior to the Doppler-shifted constant-frequency (DSCF) area. Extracellular recordings of neuronal responses from the unanesthetized animal were obtained during free-field stimulation of the ears with pure tones. FM sounds, and signals simulating their orientation sounds and echoes. Response properties of neurons and tonotopic and amplitopic representations were examined in the primary and the anteroventral nonprimary auditory cortex. In the anterior primary auditory cortex, neurons responded strongly to single pure tones but showed no facilitative responses to paired stimuli. Neurons with best frequencies from 110 to 90 kHz were tonotopically organized rostrocaudally, with higher frequencies located more rostrally. Neurons tuned to 92-94 kHz were overpresented, whereas neurons tuned to sound between 64 and 91 kHz were rarely found. Consequently a striking discontinuity in frequency representation from 91 to 64 kHz was found across the anterior DSCF border. Most neurons exhibited monotonic impulse-count functions and responded maximally to sound pressure level (SPL). There were also neurons that responded best to weak sounds but unlike the DSCF area, amplitopic representation was not found. Thus, the DSCF area is quite unique not only in its extensive representation of frequencies in the second harmonic CF component but also in its amplitopic representation. The anteroventral nonprimary auditory cortex consisted of neurons broadly tuned to pure tones between 88 and 99 kHz. Neither tonotopic nor amplitopic representation was observed. Caudal to this area and near the anteroventral border of the DSCF area, a small cluster of FM-FM neurons sensitive to particular echo delays was identified. The responses of these neurons fluctuated significantly during repetitive stimulation.

Animals↗

Effect of microtubules and intermediate filaments on mitochondrial distribution.

The laser dye rhodamine 123 specifically stains mitochondria in living cells and facilitates the observation of changes in mitochondrial distribution in single cells under a variety of experimental conditions. Visualization of mitochondria in a number of cell lines followed by processing of these cells to study different cytoskeletal elements by indirect immunofluorescence, revealed good but not absolute correlation between mitochondria and microtubules or intermediate filaments. Mitochondria and microfilament distribution within the same cell did not show such a correlation. On the basis of observations made by various experimental approaches, we suggest that mitochondrial distribution is under the strong influence of the two systems, microtubules and intermediate filaments. Neither plays an absolute role but one seems able to play a more dominant role in the absence of the other.

Animals↗

Clinical implications of large vegetations in infectious endocarditis.

Thirty-four patients with clinical infectious endocarditis were examined by M-mode and two-dimensional (2D) echocardiography. Vegetations were identified in 16 patients (47%) by M-mode and in 27 patients (87%) by 2D echocardiography. Vegetations identified by 2D echocardiography were categorized as small (less than 5 mm), medium (5 to 9 mm), or large (greater than or equal to 10 mm). Large vegetations were caused by a variety of organisms, had a higher incidence of surgery (44% v 0%), and had no increased incidence of stroke or death. The larger the vegetation, the more detectable it was by M-mode. Aortic valve vegetations were associated with a higher incidence of congestive heart failure (CHF) (67% v 14%) and stroke (44% v 9%). Four patients with large aortic valve vegetations had the highest complication rate; CHF developed in all four, two had valve replacement, one had a stroke, and two died.

Cerebrovascular Disorders↗

Functional characterization of the cells in chronic neutrophilic leukemia.

Light and electron microscopy of neutrophils from chronic neutrophilic leukemia (CNL) did not reveal differences from normal mature neutrophils. However, functional characterization of CNL cells showed marked differences when compared to normal cells. CNL neutrophils were much less viable in suboptimal conditions. Their survival was further reduced by autologous serum and was corrected by normal human serm. CNL cells showed very active phagocytosis, but their bactericidal activity was reduced in suboptimal conditions. The total content of lysozyme and beta-glucuronidase was lower in CNL cells compared to normal neutrophils, but the release of these enzymes from stimulated cells was much higher than normal. This observation is compatible with a marked lysosomal lability. Cells from the patients' peripheral blood and bone marrow showed excessive growth in CFU-C assays. Marked susceptibility of CNL cells to cytotoxic activity of cold agglutinins, SLE sera, and CSFs was observed and may signify qualitative and/or quantitative differences in the membrane structure of CNL neutrophils, as compared to normal cells.

Aged↗

Peripartum pseudomalignant myositis ossificans of the finger.

Two cases of pseudomalignant peripartum myositis ossificans of the finger are reported. The benign diagnosis is confirmed by the histologically characteristic zone phenomenon, consisting of a transition from an inner zone of proliferating spindle cells to a middle zone of well-oriented osteoid and finally to an outer zone of mature bone. In Case No. 1, because of the question of malignancy, a ray amputation was performed. In Case No. 2, the patient was observed during the peripartum period to show diminution in the size of the tumor. The lesion was eventually treated by local excision.

Adult↗

Angiolymphoid hyperplasia with eosinophilia: a bone lesion pathologically resembling Kimura's disease of skin. A report of two cases.

Primary osseous lesions morphologically identical to the soft tissue entity known as angiolymphoid hyperplasia with eosinophilia were diagnosed by means of light and electron microscopy in two men, ages 20 and 27 years, respectively. The characteristics of the lesions were reactive rather than neoplastic. The soft tissue counterpart of this lesion has shown no indication of aggressive behavior nor of a potential to metastasize. Further investigations are necessary to determine whether a similar benign behavior can be established for angiolymphoid hyperplasia with eosinophilia arising primarily in bone.

Adult↗

Laminar connections of the cat's auditory cortex.

The retrograde and the anterograde transport of horseradish peroxidase were used to study the connections established by cells in different layers of the cat's primary auditory cortex (AI). Injections of peroxidase into the medial geniculate body show that pyramidal cells in layers V and VI of AI are the sources of the corticothalamic projections. Large pyramidal cells in the outer rim of layer V also send their axons to the inferior colliculus, and it is possible that some of these cells have axons that branch to innervate both the inferior colliculus and the medial geniculate body. Cells in AI that give rise to callosal axons lie principally in layers III and VI. The callosal neurons are found in irregular clusters as wide as 1100 microgram separated by spaces that contain relatively few callosal neurons. Experiments utilizing the anterograde transport of peroxidase show that callosal terminals are found in bands running from layers VI through I. These bands are about 500 microgram in width, and the terminals seem most densely packed in layers II and III. Since the dimensions of the cell clusters and bands of callosal terminals are not the same, it is likely that not all zones which give rise to callosal axons also receive them. The bands of callosal terminals labeled by orthograde transport may be seen in the same section along with the cell bodies labeled by retrograde transport, and the two zones of label are clearly not coextensive. Complete reciprocity, therefore, seems to be absent in the callosal auditory pathway.

Animals↗

Effects of bulk pH and of monovalent and divalent cations on chlorophyll a fluorescence and electron transport in pea thylakoids.

Millimolar concentrations of monovalent cations enhance and divalent cations impede the redistribution (spill-over) of electronic excitation energy from Photosystem (PS) II to PS I in cation-depleted (sucrose-washed) thylakoids; this concept is based on chlorophyll a fluorescence and electron transport measurements over a narrow pH range around 7. We have tested the above concept in pea thylakoids over the pH range 5 to 9 by parallel measurements of various chlorophyll a fluorescence parameters (spectra, transients, and lifetimes at 77 K and 293 K, and polarization at 293 K) and of the rates of partial reactions of PSI and II. Our results provide the following information. (1) Mg2+ enhancement of fluorescence is maximum between 680 and 690 nm and minimum between 710 and 720 nm. (2) The optimum conditions for the observation of the Mg2+-induced enhancement of fluorescence are: wavelength of emission, 685 nm; concentratin of Mg2+, 10 mM, and pH, approximately 7.5. (3) Mg2+ decreases the efficiency of excitation redistribution from PS II to PS I over the pH range 6 to 9. (4) The antagonistic effects between Na+ and Mg2+ hold simultaneously for both the fluorescence intensity and lifetime, at physiological temperatures, only within the pH range 6 to 8. (5) Mg2+ enhances the light-limited electron transport rate through PS II in the pH range 5.4 to 8.2 and decreases that through PS I at pH 7.1 and 8.2. The % increase in PS II is, however, about twice the % decrease in PS I.

Cations↗

Management of children with cleft lip and palate.

Cleft lip or palate or both is one of the common congenital conditions in Ontario; its incidence is 1.2 to 1.6 per 1000 live births. A review of the records of 358 patients showed that 40%, particularly those with a severe defect, had other medical problems. This condition can affect the children and their families in many ways. In early life many patients undergo surgical repair and have speech, hearing and dental problems; during adolescence they may have cosmetic, orthodontic and emotional problems. Many parents are concerned about the genetic implications of the defect. This variety of problems requires management by several health care disciplines. Many Canadian health sciences centres offer multidisciplinary team management in a cleft palate clinic. The child's primary care physician, with whom the team exchanges information, plays a significant role in helping the child and the family function optimally.

Adolescent↗

Etiological characterization of hepatitis B surface antigen-negative hepatitis among adult patients in Athens, Greece.

In a 4-month period, 216 cases of acute viral hepatitis were diagnosed in adults at the Infectious Diseases Hospital, Athens, Greece. Twenty-six percent of these were hepatitis B surface antigen negative. A full set of clinical specimens was obtained from 19 of these patients, who were studied in depth for the etiology of their hepatitis. A total of 7 of the 19 patients had serological evidence of hepatitis A virus infection, and 2 had evidence of recent hepatitis B virus infection. The remaining 10 patients lacked evidence of hepatitis A virus, hepatitis B virus, cytomegalovirus, or Epstein-Barr virus infection related to their illness and were classified as having type non-A, non-B hepatitis. Types A and non-A, non-B hepatitis were clinically similar in these adults patients. However, patients with type non-a, non-B hepatitis were, on the average, older and more likely to have received parenteral inoculations during the 6 months before contracting hepatitis. Approximately 76% of the 216 consecutive cases of acute viral hepatitis were probably type B, approximately 10% were probably type A, and approximately 14% were probably type non-A, non-B, although the latter two types may be underestimated because of the possibility of superinfection with these viruses in asymptomatic hepatitis B surface antigen carriers. Thus, all three types of viral hepatitis appear to be important in the etiology of liver disease in Athens, Greece.

Acute Disease↗

Hepatitis type A, B, and non-A non-B in fulminant hepatitis.

Serological investigations for hepatitis B surface and e antigen, antibody to hepatitis B surface, core and e antigen and antibody to hepatitis A virus were carried out in 22 patients with fulminant hepatitis admitted to Medical Department A, Rigshospitalet, Copenhagen, in 1970-77. Nine patients had hepatitis type B and four type A. One patient had evidence of both type A and B infection, whereas the remaining eight patients showed no evidence of type A or B infection. Two of these had been treated with disulfiram and a drug aetiology could not be excluded, but in six patients no known cause of fulminant hepatitis could be determined and these patients were classified as having hepatitis type non-A non-B. The survival rate was not statistically different for patients having type A, B, or non-A non-B hepatitis.

Acute Disease↗

The role of acute hepatitis type A, B, and non-A non-B in the development of chronic active liver disease.

In 19 patients followed from biopsy-verified acute viral hepatitis to chronic active liver disease and 74 patients followed to complete resolution verified by a normal liver biopsy, sera from the acute phase were studied for serologic evidence of hepatitis type A and B. Eleven of the 19 patients who developed chronic active liver disease progressed from acute hepatitis type B and 7 from acute hepatitis type non-A non-B. One patient could not be classified because the sera were exhausted. None had serological markers of actual hepatitis type A infection. Of the 74 patients with a histologically complete resolution, the acute episode could be classified as type B hepatitis in 47 and type A hepatitis in 13 patients. The remaining 14 patients were classified as having acute viral hepatitis type non-A non-B. Our findings confirm that type B and non-A non-B hepatitis may give rise to chronic liver disease, whereas type A hepatitis so far has not been demonstrated to initiate a chronic liver disease.

Age Factors↗