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Biomedical subjects

D Hogan

Publications and source records attributed to D Hogan.

At least 37 records · Page 2Linked to original sources

A comparison of diagnosis, evaluation, and treatment of patients with dermatologic disorders.

BACKGROUND: Managed care in the American health care system may limit access to health care specialists. OBJECTIVE: We assessed primary care providers' abilities at diagnosing and treating patients with a previously undiagnosed skin disorder. METHODS: Patients with previously undiagnosed skin disorders were seen and examined sequentially by three groups of physicians: (1) internal medicine residents, (2) board-certified internal medicine attending physicians and (3) dermatology faculty. The internal medicine residents and attending physicians' diagnoses were compared with the dermatologists'. Appropriateness of therapy ordered by the internal medicine residents and attending physicians was assessed. RESULTS: Medical residents' diagnoses were correct in 43% of the patients whereas the attending physicians diagnosed 52% of cases correctly. Attending physicians and residents frequently ordered therapy inappropriate for the patient's diagnosis. Internal medicine residents and attending physicians were more likely to order skin biopsies than dermatologists. CONCLUSIONS: Our results confirm earlier studies that nondermatologists perform poorly in the diagnosis and treatment of skin disease. Primary care providers should receive more training in dermatology, or dermatologists should be permitted to act as primary caregivers to patients with skin disease.

Adult↗

Homology between Borrelia burgdorferi OspC and members of the family of Borrelia hermsii variable major proteins.

Synthesis of the Borrelia burgdorferi outer surface protein C (OspC) is quite variable. We have cloned and sequenced the ospC gene from B. burgdorferi isolate CA-11.2A, a clone in which ospC expression varies. The 5' flanking region of the gene contains at least two consensus promoter regions, as well as two large overlapping inverted repeats. Sequence comparison to other OspC proteins indicated that the CA-11.2A OspC is as closely related to OspC from two different genospecies of Lyme disease spirochetes as it is to OspC from the prototype B. burgdorferi strain, B31. Comparisons of the OspC amino acid (aa) sequence with those in aa sequence databases revealed partial identity with the variable major proteins Vmp3 and Vmp24 of B. hermsii, a causative agent of tick-borne relapsing fever. An ospC probe hybridized to B. hermsii restriction fragments and linear plasmids that also were recognized by the vmp3 and vmp24 probes. OspC and these Vmp appear to be related, but their synthesis is regulated differently in the two species of spirochetes. This represents a fascinating example of the evolution of the number, position, regulation and perhaps function of homologous genes in two related pathogens. These parameters may relate to characteristic properties of the pathogens and their separate tick vectors.

Amino Acid Sequence↗

Target recognition and visual maps in the thalamus of achiasmatic dogs.

Vision is dependent on ordered neuronal representations or maps of visual space. These maps depend on precise connections between retinal axons and their targets cells. In mammals, nerve fibres from right and left eyes produce congruent maps of contralateral visual space in adjacent layers of the lateral geniculate nucleus (LGN). We have identified an autosomal recessive mutation in Belgian sheepdogs that eliminates the optic chiasm. In these mutants, all retinal axons project into the ipsilateral optic tract, including those originating in the nasal hemiretina that normally cross midline. These animals exhibit a pronounced horizontal nystagmus. The abnormal ipsilaterally directed nasal fibres innervate the LGN as if they had successfully crossed the midline, terminating in the appropriate layer of the nucleus. As a consequence, the LGN contains non-congruent, mirror-image maps of visual space in adjacent layers. These results show that there is a robust affinity between nasal and temporal retinal axons and specific LGN layers even when all retinal axons originate from a single eye.

Animals↗

The development of parvalbumin and calbindin-D28k immunoreactive interneurons in kitten visual cortical areas.

Calbindin-D and parvalbumin are calcium binding proteins which are found in non-overlapping subpopulations of GABA-ergic interneurons in mammalian neocortex. We studied the development of these calcium-binding proteins in interneurons of cat striate and extrastriate cortical areas which have differing patterns of connectivity and follow different developmental timetables. We examined primary visual areas 17 and 18, secondary visual area 19, medial lateral suprasylvian and lateral suprasylvian areas (MLS and LLS) and association areas 7 and the splenial visual area from the day of birth (P0) through P101. Parvalbumin-immunoreactive (ir) interneurons followed the inside-out pattern of maturation of cortical laminae. They were located only in infragranular layers at the earliest ages and were not observed in the overlying cortical plate. At 3 weeks of age, when cortical lamination is mature, parvalbumin stained cells were found in all cortical layers except layer I. The number of stained secondary and tertiary dendrites in the parvalbumin-ir interneuronal population decreased with age. This change was associated with a shift in the molecular weight of parvalbumin detected on Western blots. During the first postnatal week, the area 17/18 border contained more parvalbumin-ir neurons than other visual areas. The developmental pattern of calbindin staining differed considerably from the parvalbumin staining pattern. Very few calbindin-ir interneurons were seen in area 17 during the first 2 weeks of life. In lateral cortical areas, calbindin-ir neurons were located in cortical plate, infragranular layers of cortex and white matter/subplate. Calbindin-ir neurons increased in supragranular layers of secondary cortical areas by P7 and in area 17 by P20. In the mature cortex, the calbindin staining pattern was bilaminar, with a dense band of calbindin-ir cells in layer II and a second band in layers V-VI. There was no difference in the distribution of calbindin-ir neurons among visual areas at maturity.

Animals↗

Oral premedication for local anesthesia in plastic surgery: prospective, randomized, blind comparison of lorazepam and temazepam.

Patients undergoing plastic surgical procedures under local anesthesia as inpatients were entered into a phase III randomized, blind trial designed to compare two commonly used oral premedications, lorazepam and temazepam. The effects of the drugs on each patient's memory, pain, sedation, and anxiety were assessed by questions asked of the patient, the nurse, and the surgeon. Analysis was based on 100 randomized patients. Lorazepam had a significantly greater amnesic effect (p < 0.0001), resulted in less pain with the local anesthetic injection (p = 0.006), and had a greater sedative effect than temazepam (p < 0.0001, patient's assessment; p = 0.005, observers' assessments). There was no significant difference in anxiolysis between the two premedications (p = 0.20). If premedication is indicated, we advocate the use of lorazepam rather than temazepam as premedication for plastic surgical procedures to be performed under local anesthesia, provided there is adequate postoperative supervision.

Administration, Oral↗

Plasmid location of Borrelia purine biosynthesis gene homologs.

The Lyme disease spirochete Borrelia burgdorferi must survive in both its tick vector and its mammalian host to be maintained in nature. We have identified the B. burgdorferi guaA gene encoding GMP synthetase, an enzyme involved in de novo purine biosynthesis that is important for the survival of bacteria in mammalian blood. This gene encodes a functional product that will complement an Escherichia coli GMP synthetase mutant. The gene is located on a 26-kb circular plasmid, adjacent to and divergent from the gene encoding the outer surface protein C (OspC). The guaB gene homolog encoding IMP dehydrogenase, another enzyme in the purine biosynthetic pathway, is adjacent to guaA. In Borrelia hermsii, a tick-borne relapsing fever spirochete, the guaA and guaB genes are located on a linear plasmid. These are the first genes encoding proteins of known function to be mapped to a borrelial plasmid and the only example of genes encoding enzymes involved in the de novo purine biosynthesis pathway to be mapped to a plasmid in any organism. The unique plasmid location of these and perhaps other housekeeping genes may be a consequence of the segmented genomes in borreliae and reflect the need to adapt to both the arthropod and mammalian environments.

Amino Acid Sequence↗

2-Chlorodeoxyadenosine is an active salvage therapy in advanced indolent non-Hodgkin's lymphoma.

PURPOSE: To determine the response rate to 2-chlorodeoxyadenosine (2-CdA; cladribine) in patients with advanced indolent non-Hodgkin's lymphoma (NHL) who fail to respond to or progress after a response to standard chemotherapy drugs. PATIENTS AND METHODS: Twenty-one patients were treated with at least one cycle of 2-CdA 0.1 mg/kg/d by continuous infusion for 5 or 7 days. RESULTS: The overall response rate (complete response [CR] and partial response [PR]) was nine of 21 patients (43%; 95% confidence interval, 22% to 64%). Unmaintained durable responses (longest follow-up, 29+ months) have been observed. The treatment was well tolerated by all patients. The major toxicity was related to myelosuppression (predominantly neutropenia) and immunosuppression with infection. CONCLUSION: The purine analog 2-CdA is an active salvage therapy in pretreated patients with indolent NHL, and deserves further assessment in untreated patients and in combination with other chemotherapy agents.

Adolescent↗

Postpolio syndrome in New Zealand: a survey of 700 polio survivors.

AIMS: To examine the experience of postpolio syndrome amongst a group of survivors of polio currently resident in New Zealand. METHODS: A sample of 700 responded to a request for volunteers to take part in a postal survey concerning their experience of polio and postpolio symptoms. RESULTS: The mean age of respondents was 59 years. Two-thirds of them were women. The year of polio infection was between 1915 and 1962 with the majority (54%) being in the 1945-56 period. Most were under 16 years of age (73%) at the time. Paralysis and weakness in limbs and back were the most common symptoms in the acute phase of the infection. Symptoms of the postpolio syndrome were reported by significant numbers. Increasing weakness in muscle functioning in one or more area was evident amongst 38% of the sample. Generalised muscle weakness was reported by 47%, increasing muscle wastage by 17%, difficulty swallowing by 16% and shortness of breath on waking by 10%. Pain in joints was reported by 60% and excessive tiredness by 48%. After controlling for age there was little evidence that the symptoms increased with years since the acute polio infection. CONCLUSIONS: The experience of postpolio symptoms was common amongst this group of polio survivors. It is estimated that there are between 3,000 and 5,000 polio survivors in New Zealand who may be suffering postpolio symptoms. The implications of this for primary and secondary health care provision are discussed.

Adult↗

Transient expression of calbindin-D28k immunoreactivity in layer V pyramidal neurons during postnatal development of kitten cortical areas.

Calbindin-D28k is a 28 kDa calcium binding protein that has been shown to colocalize with a specific subpopulation of gamma-aminobutyric acid inhibitory interneurons in mammalian neocortex. We have examined the ontogeny of calbindin in neonatal kitten cortex in areas 17,18,19,7, medial and lateral suprasylvian visual areas, splenial visual area and cingulate cortex from the day of birth (P0) through maturation of the brain (P101). Transient staining of immature layer V pyramidal cells was seen in kittens six weeks old and younger. This transient staining of pyramidal cells was most intense and the stained neurons were most numerous in cingulate cortex. Apical dendrites of pyramidal cells in cingulate cortex were prominently stained and could be followed to layer I, where they were seen to branch extensively. There were very few calbindin immunoreactive pyramidal cells in primary cortical areas postnatally. Transient staining in extrastriate visual cortical areas disappeared first from the lateral suprasylvian areas, and persisted longest in area 7. Pyramidal neurons in the cingulate gyrus expressed calbindin longest, but calbindin expression by pyramidal neurons ceased by the sixth postnatal week in all areas of the brain.

Aging↗

The development of somatostatin immunoreactive neurons in cat visual cortical areas.

The development of somatostatin immunoreactive (SOM-ir) neurons in cat striate and extrastriate cortex was studied to determine whether temporal changes in the morphology, distribution and density of SOM-ir neurons during development would provide clues to the emergence of specific cortical areas. The visual cortical areas examined included areas 17-19 and 7, posteromedial lateral suprasylvian, posterolateral lateral suprasylvian cortex and splenial visual area. We observed that the pattern of SOM-ir neurons in the cortical plate reflects the maturation of the cortical plate. At 1 week of age, SOM-ir neurons were only found in layers V and VI of the developing cortex; by 2 weeks of age, SOM-ir neurons were found in layer IV; and by 3 weeks of age, SOM-ir neurons were located in all layers of the cortex except layer I. SOM-ir neurons in the subplate were much more numerous under lateral cortical areas than under medial areas. This difference decreased over the first 2 postnatal weeks and by the 14th day after birth (P14), the distribution and numbers of SOM-ir neurons in the subplate/white matter had reached the adult pattern. The timing of exuberant SOM expression in the subplate suggests a function in the formation of visual corticocortical connections which begin to develop during the first postnatal week in the kitten.

Animals↗

The development of neuropeptide Y immunoreactive neurons in cat visual cortical areas.

The development of NPY-ir neurons and fibers in cat striate and extrastriate cortex was studied to determine whether temporal changes in the morphology, distribution and density of NPY-ir neurons during development would provide clues to the emergence of specific cortical areas. No differences in the number or distribution of NPY-ir neurons were observed at any age among the five visual cortical areas examined, area 17, 18, 19, posteromedial lateral suprasylvian and posterolateral lateral suprasylvian cortex. The number of NPY-ir neurons in cat visual cortical areas was higher in adult animals than in kittens. The proportion of NPY-ir neurons found in layer VIb was constant throughout life, suggesting that NPY immunoreactivity is not a marker for the transient neurons of the subplate. NPY-ir neuronal morphology was seen to 'flatten' in older animals with the development of sulci and increasing density of the brain. In contrast to the pattern observed with NPY-ir neurons, NPY-ir processes exhibited area-dependent differences during development. NPY-ir fibers grew into area 17 earlier and with a radial orientation which was not consistently observed laterally. This radial orientation was still apparent in adult brains in layer IV of area 17, though there was no orientation of fibers in the other laminae or other visual areas of the adult.

Aging↗

Development of subpopulations of GABAergic neurons in cat visual cortical areas.

The development of GABAergic interneurons in feline striate area and extrastriate areas was tracked by single and double labeling immunohistochemistry using antibodies to GABA and to molecular markers which identify subpopulations of GABAergic neurons in adult mammalian neocortex; i.e., neuropeptide Y, somatostatin, and the calcium-binding proteins parvalbumin and calbindin. The density of GABA-ir neurons was relatively constant during development and among visual areas. By contrast, most of the GABA-subpopulations increased in the cortex of visual areas during postnatal development, and thus the proportion of GABA-ir neurons which also expressed another molecular marker increased during development. By the end of the first postnatal month, the neurotransmitter phenotypes of the neocortical GABAergic neurons are mature.

Aging↗

Recombination between genes encoding major outer surface proteins A and B of Borrelia burgdorferi.

Borrelia burgdorferi causes Lyme disease, a multisystem illness that can persist in humans for many years. We describe recombination between homologous genes encoding the major outer surface proteins (Osps) A and B of B. burgdorferi which both deletes osp gene sequences and creates chimaeric gene fusions. Recombinant osp genes occur in multiple strains and encode unique proteins that lack some characteristic Osp epitopes. Antigenic variation in Osp through recombination may be relevant to the persistence of B. burgdorferi in an infected host, and has important implications for the utility of OspA and OspB as diagnostic or vaccine candidates for Lyme disease. We also describe Osp variation arising from nonsense mutations and sequence divergence, which may also represent significant sources of Osp polymorphism.

Amino Acid Sequence↗

Working group recommendations: research on content and efficacy of geriatric evaluation and management interventions.

Methods of conducting comprehensive geriatric evaluation and management (GEM) are proliferating in a variety of clinical settings. However, rigorous evaluations of efficacy for this new approach to care of older patients have demonstrated a favorable impact on patient outcome in only a few studies. All of these have been controlled single site studies, and replication is needed. If replication studies show similar results, further studies should be undertaken to define the minimum necessary intervention to achieve the desired outcome. Controlled trials are needed to determine if consultative geriatric evaluation and/or primary patient management is effective. Further innovative work is needed in model development for geriatric assessment and management in outpatient settings. Finally, studies of geriatric evaluation and management in other environments, such as home care or the nursing home, are recommended.

Forecasting↗

Polymerase chain reaction analyses identify two distinct classes of Borrelia burgdorferi.

We sequenced homologous chromosomal loci from several North American and European isolates of the Lyme disease spirochete Borrelia burgdorferi, as well as from the relapsing fever spirochete Borrelia hermsii. Inter- and intraspecies sequence comparisons permitted the design of B. burgdorferi-specific polymerase chain reaction primers that detected all strains tested (n = 31) from diverse geographical and biological origins. Polymerase chain reaction "typing" with other unique sets of primers subdivided B. burgdorferi isolates into two groups: all North American isolates and a few European isolates made up one group, while the majority of the European and Asian isolates made up the second group. This classification may have a clinical correlate reflected in differences between "typical" Lyme borreliosis in North America and Europe.

Animals↗