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Biomedical subjects

L Hoffman

Publications and source records attributed to L Hoffman.

At least 73 records · Page 4Linked to original sources

Monitoring the axilla in patients with silicone gel implants.

Migration of silicone beyond the breast implant capsule may occur as a result of silicone bleed, leak, or rupture, and it may indicate failure of implant envelope integrity. We report a series of 23 patients with silicone implants who had axillary lymph node biopsies for palpable masses. Group 1 (n = 15) had biopsies performed an average of 6 years following aesthetic augmentation, and Group 2 (n = 8) had biopsies performed an average of 5 years after mastectomy reconstruction. All biopsies demonstrated foreign body reaction consistent with silicone migration. Five patients in Group 1 and two in Group 2 also had breast cancer detected by the axillary biopsy. Evaluation of the axilla utilized a combination of one or more techniques, including mammography, ultrasonography, magnetic resonance imaging, and fine-needle aspiration. We conclude that (1) routine evaluation of the axilla is mandatory in all patients with silicone breast implants; (2) an algorithmic approach in diagnosing axillary masses may be helpful, especially in augmentation patients; and (3) axillary masses detected by clinical examination or other means must be biopsied, even in the face of negative screening studies, because breast cancer may be coincidental with a silicone granuloma.

Adult↗

Complete nasal agenesis with bilateral microphthalmia and unilateral duplication of the thumb.

Complete nasal aplasia is an extremely rare clinical entity and most infants are stillborn when this is associated with holoprosencephaly. A viable 3-year-old infant born with frontonasal arrest without holoprosencephaly is presented. The child's main complaint was lack of a nasal airway, which made eating extremely difficult. A method for craniofacial reconstruction of the nasopharynx is presented.

Abnormalities, Multiple↗

Maturation and migration of cutaneous dendritic cells.

Dendritic cells have been isolated from the epidermis, dermis, and lymphatics of skin. Cells from each cutaneous compartment can exhibit the distinct morphology, surface phenotype, and strong T-cell-stimulating activity of dendritic cells that are isolated from other organs. Of importance are the mechanisms by which the maturation and movement of dendritic cells are regulated within intact tissues. Epidermal dendritic cells turn over slowly in the steady state. Stimuli, including contact allergens and transplantation, perhaps by inducing a release of cytokines such as granulocyte macrophage-colony-stimulating factor, mobilize these dendritic cells into the dermis and lymph. This migration is accompanied by the maturation of dendritic cell functions; e.g., antigen-presenting major histocompatibility complex molecules and B7 costimulators increase markedly. On the other hand, there is a sizable, steady-state flux of dendritic cells in afferent lymph draining the skin, which suggests a constant traffic through the dermis that is independent of sessile epidermal dendritic cells. When explants of skin are placed in organ culture, dendritic cells emigrate into the medium for 1-3 d. The dendritic cells are mature and can bind tightly to small memory T cells that also migrate in these cultures. The emigrated mixtures of dendritic cells and T cells should be useful in the study of many clinical states. This is illustrated by recent experiments showing that migratory skin cells are readily infected with human immunodeficiency virus (HIV)-1. A strong productive infection takes place in the absence of exogenous cytokines, foreign sera, or mitogens or antigens. The dendritic cell-T-cell conjugates are the essential site for infection. This cellular milieu may model events during the sexual transmission of HIV-1, where relevant mucosal surfaces are covered by skin-like epithelia. The capture of CD4+ memory T cells by dendritic cells may explain the chronic drain of immune memory in HIV infection.

Animals↗

Both dendritic cells and memory T lymphocytes emigrate from organ cultures of human skin and form distinctive dendritic-T-cell conjugates.

Prior studies of mouse skin in organ culture have shown that dendritic cells selectively emigrate from the explants over 1-3 d. This emigration may model the movements of dendritic cells that can occur in situ, as in transplantation and contact sensitivity. In this study, we cultured explants of normal human skin that had been removed with a dermatome. Dendritic cells with characteristic morphology and mixed leukocyte response-stimulatory activity emigrated. The dendritic cells had the expected phenotype, e.g., rich in major histocompatibility complex class II and accessory molecules such as B7-1, intercellular adhesion molecule-1, and leukocyte function-associated antigen-3. Small lymphocytes also were present in the emigrated populations and proved to be T cells exclusively, almost entirely of the TcR alpha beta and memory type (CD45RAweak, CD45RO LFA-3/CD58+), with a CD4:CD8 subset ratio of about 2:1. Some of the T cells were bound tightly to the dendritic cells. These conjugates did not dissociate after exposure to trypsin or to calcium- and magnesium-free medium, or during cytofluorography. This made it possible to sort distinct populations of single dendritic cells, single T cells, and conjugates of the two cell types. Conjugates would continue to form from mixtures of separated dendritic cells and T cells in culture. Therefore, cutaneous dendritic cells and memory T lymphocytes emigrate from human skin explants, and some of these cells form distinctive conjugates that we hypothesize contribute to immunologic recall reactions.

Cell Communication↗

Crescentic glomerulonephritis and eosinophilic interstitial infiltrates in a patient with hypereosinophilic syndrome.

Crescentic glomerulonephritis with immune complex deposition and acute eosinophilic interstitial nephritis developed in a patient with the hypereosinophilic syndrome. Acute renal failure ensued but was rapidly reversed by high-dose oral prednisone. Confounding factors and unusual findings are described with a review of recent literature. This mode of presentation has not previously been reported.

Acute Disease↗

Conjugates of dendritic cells and memory T lymphocytes from skin facilitate productive infection with HIV-1.

Experimentally, a productive infection with HIV-1 requires that virus be administered to T cells that are activated by mitogens. We describe a productive milieu for HIV-1 within the confines of normal skin that does not require standard stimuli. The milieu consists of dendritic cells and T cells that emigrate from skin and produce distinctive stable, nonproliferating conjugates. These conjugates, upon exposure to each of seven different HIV-1 isolates, begin to release high levels of virus progeny within 4 days. Numerous infected syncytia, comprised of both dendritic and T cells, rapidly develop. We propose that conjugates of dendritic cells and T cells, as found in the external linings of organs involved in sexual transmission of HIV-1, represent an important site for the productive phase of HIV-1 infection. Because the affected T cells carry the memory phenotype, this site additionally provides a mechanism for the chronic depletion of CD4+ memory cells in HIV-1 disease.

CD4-Positive T-Lymphocytes↗

Activation of the multicatalytic protease. The 11 S regulator and 20 S ATPase complexes contain distinct 30-kilodalton subunits.

The multicatalytic protease (MCP) associates with a 20 S ATPase complex in the presence of ATP to form the 26 S ubiquitin/ATP-dependent protease. This association results in a uniform 3-fold activation of peptide hydrolysis by MCP. In the absence of nucleotides, an 11 S regulator binds MCP and differentially stimulates its peptidase activities from 3-fold to 25-fold depending upon the peptide. When incubated separately with ATPase complex or regulator, all MCP molecules are converted to 26 S protease or to an activated MCP, respectively. Competition between ATPase complex and regulator for limiting amounts of MCP results in the 26 S protease as the only assembled species. Rabbit reticulocyte regulator is composed of a single 30-kDa protein. Among the 15 subunits in the ATPase complex, there is also a 30-kDa protein. Three findings demonstrate that the 30-kDa subunits in each complex are distinct proteins. First, two-dimensional polyacrylamide gel revealed different isoelectric points for each 30-kDa protein. Second, anti-regulator antibodies did not cross-react with proteins in the ATPase complex or in the 26 S protease. Third, directly sequenced peptides from the 30-kDa subunit of the ATPase complex are not present in the deduced amino acid sequence of the regulator. Thus, the regulator and ATPase complex are independent activators of MCP.

Adenosine Triphosphatases↗

Staged approach to combined repair of pectus excavatum and lesions of the heart.

The combined repair of severe pectus excavatum and cardiac lesions remains technically difficult. We report our experience with a patient undergoing such a combined repair of pectus and implantation of an aortic valved conduit in the setting of the Marfan syndrome. The procedure was staged such that the dissection and bony mobilization was done at the first procedure before heparin administration in combination with a sternal split and subsequent aortic repair. The second stage of sternal repositioning and cartilage resection was completed several days later with excellent cardiopulmonary and cosmetic results. The technique and a review of the literature are included.

Adult↗

Use of tissue expanders in final reconstruction of infrapubic midline scar, mons pubis, and vulva after bladder exstrophy repair.

Two patients following bladder exstrophy repair presented for final cosmetic reconstruction with the characteristic lower abdominal midline scar, bisected mons pubis, and laterally displaced labia majora. Tissue expanders were used to obtain additional skin and subcutaneous tissue. After adequate serial expansion, the expanders were removed, scar tissue excised, and primary approximation of healthy tissues performed. A tension-free closure and esthetically pleasing midline incision, mons pubis, and vulva were obtained.

Adolescent↗

Morphologic and quantitative study of the efferent vestibular system in the chinchilla: 3-D reconstruction.

An HRP study of the EVN has been performed. Three groups of somas have been identified: Those located in the proximity of the vestibular nuclei, those sandwiched between the facial genu and the IVth ventricle, and those in the RF, surrounding the abducens nucleus. The number of somas is greater in the contralateral brain-stem side. Axons could be followed through the midline, but could not be traced to a labelled soma. A 3-D reconstruction of the EVN within the brain stem is presented.

Animals↗

Psychopharmacology in the treatment of anorexia nervosa and bulimia nervosa.

Anorexia nervosa and bulimia nervosa remain enigmatic disorders with poorly understood etiologies. Clinicians continue to find these disorders very challenging to treat. As their underlying pathophysiology is clarified, it is hoped that specific pharmacologic treatments will be developed to alleviate the pain and disability these disorders produce.

Anorexia Nervosa↗

Multiple forms of the 20 S multicatalytic and the 26 S ubiquitin/ATP-dependent proteases from rabbit reticulocyte lysate.

We have used native gel electrophoresis followed by fluorogenic peptide overlay to identify multiple forms of rabbit reticulocyte multicatalytic protease (MCP) or 20 S protease, and two forms of rabbit 26 S ubiquitin/ATP-dependent protease. An abundant, fast-migrating 20 S complex (20 SF) possesses modest ability to hydrolyze the fluorogenic peptide succinyl-Leu-Leu-Val-Tyr-4-methyl-coumaryl-7-amide. In contrast, two minor, slower migrating species cleave the peptide at high rates. A unique 30-kDa polypeptide is associated with one of the active MCPs, and a 160-kDa subunit is associated with the other. Two electrophoretically distinct 26 S proteases can also be isolated from rabbit reticulocyte lysate. The faster migrating form, 26 SF, is more resistant to inactivation by ATP depletion. Despite the differential response to nucleotides and the distinctive electrophoretic mobilities of 26 SF and 26 SS, we have not identified any subunit differences between the two enzymes. In addition to active 26 S proteases, we have discovered and purified a proteolytically inactive particle that contains subunits characteristic of the 26 S protease (e.g. molecular masses between 30 and 110 kDa). Incubation of this protein complex with purified MCP and ATP results in the formation of the 26 S proteases.

Adenosine Triphosphate↗

The effect of drug exposure on thyroid hormone levels of newborns.

This study examines the effect of women's alcohol abuse during pregnancy on the thyroid-stimulating hormone (TSH) and thyroxine (T4) levels of their babies at birth. Forty-seven babies were born to mothers identified as substance abusers. Maternal use of marijuana and/or cocaine did not result in newborns' TSH and T4 hormone levels being significantly different from non-substance-abusing controls' TSH and T4 levels. Alcohol use, however, was significantly linked to lower newborn TSH levels, lower than TSH levels of a control sample of newborns whose mothers used marijuana and/or cocaine, and lower than a control sample of newborns whose mothers abused no substances. This finding suggests further investigation of possible links between thyroid functioning and fetal alcohol syndrome (FAS).

Alcoholism↗

Variations in digital nerve anatomy.

One hundred digital nerves from 10 cadaver hands were dissected, and branching patterns were analyzed. Contrary to the traditional belief that the digital nerve predictably trifurcates at the distal interphalangeal crease, much variation exists. Terminal branching occurred distal to the crease in 60% of the thumb digital nerves and in 78% of the digital nerves supplying the other four digits. The number of terminal branches also varied from two to seven in the thumb and from two to five in the other four digits. No significant differences were seen in branching patterns between digits or between radial and ulnar sides. These findings are clinically relevant to the surgeon who is contemplating digital nerve repair.

Cadaver↗

On the clinical utility of the concept of depressive affect as signal affect.

The author reviews the scant literature relating to the concept of depressive affect as an affect parallel to anxiety. Then, through the presentation of detailed clinical psychoanalytic data, in particular the patient's associations to interpretation, he demonstrates the value to the conduct of a psychoanalysis of an awareness of the role of depressive affect as a signal affect that triggers defense.

Anxiety↗

Constructing realities: an art of lenses.

In this essay I attempt to map the dimensions of my own move away from a cybernetic-biologic analogy for "family-systems" therapy. Central to this shift has been social construction theory augmented by two other lenses: a second-order view, and a sensitivity to gender. These conceptual tools have helped me to distance myself from my previous therapeutic stance and to envision a very different model, one that is less strategic and instrumental, and more collaborative and unconcealed.

Cognition↗