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Biomedical subjects

M Joseph

Publications and source records attributed to M Joseph.

At least 91 records · Page 5Linked to original sources

Clinical and laboratory correlates of human immunodeficiency virus infection in a cohort of intravenous drug users from New York, NY.

BACKGROUND: The human immunodeficiency virus (HIV) epidemic has increasingly involved intravenous drug users. Few studies have attempted to define its clinical and laboratory characteristics in this population. METHODS: We recruited 223 intravenous drug users from New York, NY, for a prospective study of the natural course of HIV infection. Medical history, physical examination, medical staging, and immunologic assessments were performed at 6-month intervals. We examined the baseline findings among this cohort. RESULTS: Of the total cohort, 65.9% were men and 34.1% were women, with 70.9% African American, 12.6% white, 11.7% white Latino, and 4.9% black Latino. At baseline, 44.4% were HIV negative and 55.6% were HIV positive. No significant association was noted between ethnicity, gender, and serologic status. Also no significant difference was noted for homelessness either across serologic status or gender. There was a trend toward an association between gender and use of drugs during the week before interview; the women showed higher drug use. A significant association was noted between HIV serologic status and reported history of pneumonia, oral candidiasis, cough, night sweats, fever, and lymphadenopathy on physical examination. In a regression model, white blood cell count, hematocrit, symptom/sign complex score, and CD4 cell number were significantly associated with HIV status. CONCLUSION: This study provided important historical, clinical, and immunologic characteristics that are useful in the identification and evaluation of the HIV-infected intravenous drug user.

Analysis of Variance↗

Unfolding of lysozyme by breaking its disulphide bridges results in exposure of hydrophobic sites.

The interaction of 1-anilino-naphthalene-8-sulphonate (ANS), a probe whose fluorescence is strongly dependent on hydrophobicity of the environment, with native lysozyme and lysozyme partially unfolded by breaking the disulphide bridges and reacting the free -SH groups with iodoacetamide, has been investigated. Monitoring the intensity of ANS fluorescence and the position of the emission maximum in the presence of native and partially unfolded lysozyme indicated that unfolding resulted in the exposure of hydrophobic sites. Hydrophobic sites could not be detected when native and partially unfolded lysozyme were denatured with urea or guanidinium chloride. Protein components of the cells export machinery like 'chaperones' associate only with partially unfolded proteins and not native, folded proteins. Hence, hydrophobic regions of proteins, exposed on partial unfolding, could be the sites of recognition by 'chaperone' proteins.

Anilino Naphthalenesulfonates↗

Using a claims database to investigate drug-induced Stevens-Johnson syndrome.

In order to explore a priori hypotheses about drug-induced Stevens-Johnson Syndrome (SJS), a case-control study was initiated using data from COMPASS, a computerized data base consisting of Medicaid claims data. The records of 3.8 million patients in five U.S. states were searched to identify patients with an inpatient diagnosis of ICD-9-CM code 695.1 (erythema multiforme-EM). Out of the total of 367 cases that were identified, primary medical records for 249 were sought and 128 (51.4 per cent) of these were obtained. The remainder could not be obtained because: in 36 (29.8 per cent) the hospital refused to provide medical records; in 33 (27.3 per cent) there were transcription errors; in 20 (16.5 per cent) the state could not translate the identification number, primarily because the patients lost Medicaid eligibility too long before our request; in 27 (22.3 per cent) the hospital could not locate the patient's record; and in 5 (4.1 per cent) there were other reasons. Of those with a medical record, 121 (94.5 per cent) had a skin diagnosis and 109 (85.2 per cent) had a diagnosis compatible with ICD-9-CM code 695.1 specified on their discharge summary. However, in 35 (27.3 per cent) an expert reviewer felt that the discharge diagnosis was incorrect. In 50 (39 per cent) the computer diagnosis was incorrect. Only 19 (14.8 per cent) were judged by the expert reviewer to truly have Stevens-Johnson Syndrome, and an additional 37 (28.9 per cent) were judged to have erythema multiforme minor. Thus, the computerized diagnosis agreed very well with the diagnoses specified on the discharge summary. However, EM is frequently misdiagnosed, ICD-9-CM code 695.1 contains multiple other diagnoses which are not EM, and much of hospitalized EM is EM minor. Thus, studies of SJS cannot be performed except in patients whose medical records are available.

Adolescent↗

Increased secretion of tumor necrosis factor alpha and interleukin-6 by alveolar macrophages consecutive to the development of the late asthmatic reaction.

The late asthmatic reaction (LAR), consecutive to bronchial allergen challenge, is characterized both by the influx of various cells in proximal and distal airways and by the enhancement of bronchial hyperresponsiveness. However, the exact conditions for the development of the inflammatory reaction during the LAR remain to be specified. Since monokines play a key role in inflammatory processes, particularly in the lung, the production of tumor necrosis factor-alpha (TNF-alpha), interleukin; 1-beta (IL-1-beta) and interleukin-6 (IL-6) by alveolar macrophages (AM), collected 18 to 20 hours after exposure to allergen, was evaluated in 15 allergic subjects with asthma submitted to a challenge test with Dermatophagoides pteronyssinus (N = 6) or with wheat flour (N = 9) and in three healthy subjects. After bronchial provocation test, four patients presented no bronchial response (group 1), and six patients, a single early reaction (group 2). In contrast, five patients developed successively an immediate plus a late response (group 3). The monokine production was compared to that from nine allergic subjects with asthma studied at baseline (group 0) and from 11 unchallenged healthy subjects (control subjects). Measurements of cytokines were evaluated for TNF-alpha and IL-1-beta by a specific immunoradiometric assay, whereas IL-6 levels were appreciated by the proliferation of 7TD1 cells. No detectable amounts of TNF-alpha, IL-1-beta, and IL-6 were in bronchial alveolar lavage fluid, even after a tenfold concentration. In contrast, a significant increase of TNF-alpha (10,642 +/- 3127 U/ml) and IL-6 (1250 +/- 427 U/ml) concentrations was noted in AM supernatants from patients exhibiting an LAR (group 3) compared to cells recovered from groups 2, 1, and 0 and to challenged or unchallenged control subjects (805 +/- 244, 995 +/- 521, 1269 +/- 524, 688 +/- 85, and 445 +/- 74 pg of TNF-alpha per milliliter, respectively; 190 +/- 64, 114 +/- 91, 242 +/- 95, 80 +/- 9, and 54 +/- 19 U/ml of IL-6 per milliliter, respectively). No modification of IL-1-beta contents could be detected between the different groups. A significant correlation was detected between concentrations of TNF and IL-6 (r = 0.92; p less than 0.001). These results demonstrate TNF-alpha and IL-6 secretion by AM consecutively to the development of LAR in allergic subjects with asthma, confirming that AMs are activated after allergen challenge.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Botulinum A toxin for the treatment of adult-onset spasmodic torticollis.

Thirty-five patients with adult-onset idiopathic torticollis were treated by local injections of botulinum A toxin into dystonic cervical muscles. Substantial improvement with respect to reduction and elimination of pain was found in 81 percent, improvement in posture deformity and involuntary spasms in 70 percent, increased range of motion of the neck in 78 percent, reduction in visible sternocleidomastoid hypertrophy in 86 percent, and improvement in tremor in 65 percent. The syndrome was divided into four subtypes based on pattern of dystonic muscle groups involved in the dystonia, head and shoulder posture, and sternocleidomastoid muscle hypertrophy. Injection strategy based on this subdivision is described.

Adult↗

Effects of Furegrelate (Upjohn 63557A) on patency and platelet deposition after canine carotid endarterectomy.

Platelet deposition upon endarterectomy sites is a likely cause for early postoperative thrombosis, embolism and restenosis. Platelets aggregate by the thromboxane-prostacycline mechanism. Thromboxane synthetase inhibitors which have been safely administered to humans should reduce platelet deposition after surgical therapy and therefore reduce peri-operative mortality and the prevalence of stroke. A randomized prospective controlled trial was designed to determine vessel patency and platelet deposition associated with the use of 3 mg/kg and 30 mg/kg of Furegrelate (Upjohn U63557A) daily in dogs, who were to have carotid endarterectomy. The 46 treated and 46 control dogs had total carotid patency of 96% and 76% respectively (P less than 0.01). Fourteen dogs treated with 30 mg/kg Furegrelate had no occlusions, compared with a 19% prevalence in 13 controls (P less than 0.02). Furegrelate 10 mg/kg significantly lowered platelet aggregation. Platelet deposition was not significantly changed, however. The reason for this disparity was a probable persistence of vessel wall factors which promoted platelet deposition. This approach might therefore lower rates of peri-operative thrombosis but it would be very unlikely to alter the incidence of restenosis or embolism. Further research could be directed towards modifying the stimuli for platelet deposition upon the endarterectomy site.

Animals↗

Interaction of SR 33557 with skeletal muscle calcium channel blocker receptors in the baboon: characterization of its binding sites.

A procedure for the isolation of primate skeletal microsomal membranes was initiated. Membranes exhibited specific enzymatic markers such as 5'-nucleotidase, Ca++,Mg(++)-adenosine triphosphatase and an ATP-dependent calcium uptake. Baboon skeletal microsomes bound specifically with high-affinity potent Ca++ channel blockers such as dihydropyridine, phenylalkylamine and benzothiazepine derivatives. Scatchard analysis of equilibrium binding assays with [3H](+)-PN 200-110, [3H](-)-desmethoxyverapamil [( 3H](-)-D888) and [3H]-d-cis-dilitiazem were consistent with a single class of binding sites for the three radioligands. The pharmacological profile of SR 33557, an original compound with calcium antagonist properties, was investigated using radioligand binding studies. SR 33557 totally inhibited the specific binding of the three main classes of Ca++ channel effectors and interacted allosterically with them. In addition, SR 33557 bound with high affinity to a homogeneous population of binding sites in baboon skeletal muscle.

5'-Nucleotidase↗

A population-based study of Stevens-Johnson syndrome. Incidence and antecedent drug exposures.

To determine the incidence of Stevens-Johnson syndrome, a descriptive epidemiology study was performed using computerized Medicaid billing data from 1980 to 1984 from the states of Michigan, Minnesota, and Florida. The ratio of persons hospitalized with a discharge diagnosis of erythema multiforme (ICD-9-CM code 695.1) to persons with any claim for medical service was first used as an estimate of the incidence rate of the disease. Then, since the ICD-9-CM code for erythema multiforme includes other illnesses in addition to Stevens-Johnson syndrome and because these illnesses are frequently misdiagnosed, the information provided by a review of medical records for a subset of cases of erythema multiforme was used to determine the proportion of patients with true Stevens-Johnson syndrome. The incidence rates of Stevens-Johnson syndrome were 7.1 (6.1 to 8.2), 2.6 (1.6 to 4.0), and 6.8 (4.3 to 10.3) per million per year in each state, respectively. Penicillins, especially aminopenicillins, were frequently used in the 19 patients judged to be true cases of Stevens-Johnson syndrome. In conclusion, Stevens-Johnson syndrome is a uncommon condition. The excess risk of Stevens-Johnson syndrome due to any drug must, therefore, be very low.

Adolescent↗

Lymphocyte-mediated inhibition of platelet cytotoxic functions during Hymenoptera venom desensitization: characterization of a suppressive lymphokine.

Recently, it has been shown that platelets, through a receptor for the Fc fragment of IgE, could be specially triggered by venom allergens in hypersensitivity to hymenoptera, generating cytocidal mediators toward Schistosoma mansoni larvae, and oxygen metabolites measured by chemiluminescence. After rush immunotherapy, a depressed platelet response was demonstrated to be associated with the production of lymphokine(s). Here we report the characterization of a factor present in supernatants of antigen-stimulated T cells from patients after hymenoptera venom desensitization which is able to inhibit platelet cytotoxic functions in a dose-dependent manner. The optimal inhibition was observed with supernatants obtained after T lymphocyte stimulated with 10(-5) micrograms venom allergen/ml. Once specifically produced the platelet-suppressive effect of lymphocyte supernatants was not antigen specific. The producing T cell subpopulation was identified as CD8+. This lymphokine had an approximate molecular mass of 25 kDa and a pI of 4.8. It was heat and acid stable and sensitive to trypsin and proteinase K but not to neuraminidase. This platelet inhibitory activity was absorbed by platelet membrane suggesting its binding to a receptor. These properties were very similar to a previously described platelet activity suppressive lymphokine, suggesting the participation of this lymphokine in the mechanisms of rush desensitization.

Animals↗

Role of phospholipase A2 and G-proteins in the IgE-dependent activation of mast cells and macrophages.

The effect of para-bromophenacyl bromide (a selective inhibitor of phospholipase A2) and pertussis toxin has been investigated on IgE-dependent histamine release and on IgE-dependent macrophage-mediated cytotoxicity. Para-bromophenacyl bromide inhibited dose-dependently IgE-dependent stimulation of mast cells and macrophages (IC50's of 5.0 X 10(-7) M and 2.5 X 10(-7) M, respectively). In contrast, pertussis toxin only inhibited the IgE-dependent stimulation of macrophages, whereas the IgE-dependent activation of mast cells was not affected. These results suggest that the transducing mechanisms following the activation of the high affinity receptor for IgE (Fc epsilon RI on mast cells) as well as the low affinity receptor for IgE (Fc epsilon RII on macrophages) induce the activation of phospholipase A2. Fc epsilon RII might be coupled to a pertussis toxin sensitive G-protein.

Acetophenones↗

Prehospital cricothyrotomy: an investigation of indications, technique, complications, and patient outcome.

The records of all patients who presented to a Level 1 trauma center during a two-year period for whom a prehospital cricothyrotomy was attempted or ordered were reviewed. Twenty patients met the study criteria. The average age was 37 years (range, 11 to 65 years). Indications for prehospital cricothyrotomy were massive facial trauma (eight), failed oral intubation (seven), and suspected cervical-spine injury (one). Cricothyrotomy was attempted in 16 patients (80%), with the remaining four having the procedure ordered but not attempted. A successful airway was achieved in 14 patients (88%). Horizontal incisions were used in all cases and were anatomically correct in 15 of 16 attempts (94%). The overall immediate complication rate was 31%. Two patients (12%) sustained major complications (failure to obtain an airway). No hemorrhagic complications occurred, but 16 of the 20 were in cardiac arrest in the field. Long-term complications were not evaluated. All patients sustained major injuries (mean Injury Severity Score, 53.7), except one patient who suffered airway obstruction from food. Three patients (15%) survived; two of the three suffered permanent, severe brain dysfunction. These preliminary findings demonstrate that prehospital cricothyrotomy is being used chiefly in massively injured patients who are already beyond recovery. It is thus difficult to assess whether the procedure is either safe or effective. There is a need for further investigation to determine whether prehospital cricothyrotomy has any beneficial effect on outcome and, if so, in what setting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The abnormal in vitro response to aspirin of platelets from aspirin-sensitive asthmatics is inhibited after inhalation of nedocromil sodium but not of sodium cromoglycate.

1. Blood platelets from patients with aspirin-sensitive asthma (ASA) generated cytotoxic mediators in the presence of aspirin. This abnormal in vitro response to aspirin was abolished within 1 h after nedocromil sodium inhalation but not after sodium cromoglycate inhalation. 2. Platelets recovered this reactivity to aspirin by 12 hours after nedocromil sodium treatment of ASA-patients. 3. The in vitro reactivity to aspirin of ASA platelets isolated before inhalation was inhibited in the presence of serum isolated 15 and 60 min after nedocromil sodium inhalation.

Administration, Inhalation↗

Short-term decrease of skin-test sensitivity after rush desensitization in Hymenoptera venom hypersensitivity.

Thirty-seven patients with a history of systemic anaphylactic stings were desensitized by the rush method. Patients were evaluated by skin testing twice, before and 6 weeks after desensitization. An additional control group of 10 patients, not yet desensitized, were tested for skin test technique reproducibility at 6-week intervals. Results were compared with IgE and IgG antibody levels, and with platelet reactivity towards specific Hymenoptera venom. Before desensitization, the maximum skin-test sensitivity was observed at 10(-5) micrograms venom/ml in 56% of patients and decreased to 10(-1) micrograms venom/ml after desensitization (48.6% of patients). Decrease of cutaneous tests was observed in 28/37 patients (75%) (P less than 0.001) and was not associated with significant variations of specific IgE or IgG antibody levels, but was correlated with the decrease of platelet reactivity (P less than 0.05). Conversely, variations of skin-test sensitivity in the control group was not significant.

Adolescent↗

Plasmapheresis in a patient with severe asthma associated with auto-antibodies to platelets.

Although the pathogenesis of aspirin-sensitive asthma remains to be specified, it is known that in the presence of acetylsalicylic acid or non-steroidal anti-inflammatory drugs, platelets from aspirin-sensitive asthmatics have been described as generating cytocidal mediators that killed parasite targets such as Schistosoma mansoni larvae. Here we report, in a patient with corticosteroid-dependent asthma associated with aspirin sensitivity, the presence of circulating IgE antibodies against 55 kD and 68 kD platelet antigens. In addition, the serum from this patient was shown to contain a factor able to trigger the release of cytocidal mediators from his platelets as well as from normal individual platelets. This platelet stimulatory activity was presumably supported by IgE antibodies or immune complexes. After informed consent the patient was submitted to plasma exchanges. Plasma removal induced clinical improvement, anti-platelet antibody decrease, and the reduction of the platelet stimulatory activity. All clinical symptoms disappeared within 2 weeks. The disease remained quiescent for 2 months, and daily requirements for prednisone (20-5 mg), and beta-agonist (10-16 to 0-1 inhalations) could be kept at a low level follow-up. The plasma exchanges were delayed by 3 mg kg-1 azathioprine with the maintenance of clinical improvement. A relapse occurred after the arrest of immunosuppressive therapy with the reappearance of both asthma attacks and anti-platelet antibodies, as well as the increase of the platelet stimulatory activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Microcomputer database and system of audit for the vascular surgeon.

We have set up a vascular database based upon an IBM personal computer in the vascular unit at Repatriation General Hospital, Concord, using 'Dataease'. This is commercially available software that allows the development of a database by users with little or no programming knowledge. The database is menu driven and designed to record details of admissions, indications for surgery, operations, complications and follow-up and has been set up as a prospective project from 1 January 1989 after a pilot study in 1988. Currently, interns, residents and registrars enter data directly onto the computer, providing an excellent teaching and review medium. Unit audit is easy as the program is completely menu driven and there are more than 100 customized reports written, ranging from providing simple complication details to complex reports deriving graft cumulative patency rates. This system also provides for 'instant' discharge letters which have markedly improved communication with the general practitioner.

Hospital Information Systems↗