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Biomedical subjects

R David

Publications and source records attributed to R David.

At least 37 records · Page 2Linked to original sources

Hyperparathyroidism with normal albumin-corrected total calcium in patients with multiple endocrine neoplasia type 1.

In the largest reported family of patients with multiple endocrine neoplasia type 1 (MEN 1), hyperparathyroidism was expressed at first screening in 33 patients by elevation of ionized calcium (IC) (30 cases) or parathyroid hormone (three cases) without elevation of albumin-corrected total calcium (ACTC). Three of these 33 patients have shown a progressive rise in IC and later an elevation of ACTC. However, the age distribution suggests that in others the level of IC may remain stable at a minimally elevated level throughout life with ACTC remaining normal except for transient rises at the times of intercurrent illness or surgical operation. Even when ACTC is normal preoperatively, patients with an elevation of IC require radical subtotal parathyroidectomy or total parathyroidectomy and forearm implantation to restore IC to a normal level. Institutions that rely on ACTC as a screening test for hyperparathyroidism in MEN 1 will miss the diagnosis in nearly half of patients under the age of 30. The greatest deficiency in using ACTC occurs in the follow-up of patients who have undergone parathyroidectomy for MEN 1. Only three of 11 recurrences were evidenced by this measurement.

Adolescent

Spontaneous hyphema: an unusual complication of uveitis associated with ankylosing spondylitis.

Two patients with ankylosing spondylitis (AS) and recurrent uveitis had rubeosis iridis each with an episode of spontaneous hyphema. Rubeosis iridis has been reported to occur in some cases of uveitis, but it has not been seen in those associated with AS. We suggest that AS be included among the conditions that can lead to the development of rubeosis iridis, with consequent silent hyphema.

Adult

Identification of a major human immunodeficiency virus-1 reverse transcriptase epitope recognized by mouse CD4+ T lymphocytes.

Delineation of major T helper cell recognition sites of human immunodeficiency virus (HIV-1) proteins represents one important step in the design of an efficient acquired immune deficiency syndrome (AIDS) vaccine. Towards this end, we have explored the immunogenicity of HIV-1BRU proteins in the mouse model. Preliminary experiments revealed that inbred mice primed with whole inactivated HIV-1 developed strong CD4+ T cell proliferative responses to a variety of recombinant viral proteins including reverse transcriptase (RT). To characterize further the mouse T cell responses to this protein, several Ad- or Ed-restricted T hybridoma cells (THC) were established from BALB/c or DBA/2 mice. These THC were tested for their capacity to recognize a series of 15-mer synthetic overlapping peptides spanning three segments of HIV-1 RT that had been preselected on the basis of either alpha-helicity, amphipaticity, and/or for containing rare amino acid sequence patterns. Peptides corresponding to a C-terminal region (residues 528-560) of RT were recognized by several of the THC established from RT-primed mice. Furthermore, a non-alpha-helical peptide from this region (A3, 528-543) was capable of priming mice with different H-2 haplotypes for both peptide A3 and native RT CD4+ T cell recognition. In addition to the recently identified RT determinant 203-219 capable of triggering both mouse and human CD8+ CTL, the present results identify a good candidate for an immunodominant RT epitope capable of eliciting RT-specific T helper cell responses.

Animals

The calcaneus: normal and abnormal.

The calcaneus is the largest tarsal bone. Many congenital and acquired disorders affect the bone. Primary disorders arise in the calcaneus itself, whereas secondary disorders arising in the neighboring soft tissues extend into and affect the calcaneus indirectly. Among the primary lesions, congenital, traumatic, infectious, hematologic, neoplastic, and other miscellaneous disorders constitute the majority, whereas various arthritides and soft-tissue neoplasms that arise adjacent to the bone constitute the important secondary calcaneal disorders. Radiographic features of many disorders of the calcaneus are disease-specific and thus diagnostic. This article describes a wide spectrum of calcaneal disorders and illustrates their salient radiographic features. This knowledge should facilitate radiographic diagnosis of various calcaneal disorders encountered in clinical practice.

Bone Diseases

Suppression of the pituitary-gonadal axis in children with central precocious puberty: effects on growth, growth hormone, insulin-like growth factor-I, and prolactin secretion.

To assess further the relationship between gonadal sex steroids and PRL, GH, and insulin-like growth factor-I (IGF-I) secretion and to help clarify the mechanism underlying the pubertal growth spurt, we studied 11 children (10 girls) with central precocious puberty before and during gonadal suppression with the GnRH agonist (GnRH-a) leuprolide acetate. Nocturnal sampling for plasma levels of GH and PRL, GH response to GH-releasing factor-(1-44), and plasma IGF-I levels were determined before and 3-6 months after pituitary-gonadal suppression. Treatment caused a significant decrease in the LH and FSH responses to GnRH (P less than 0.01) and the plasma concentration of estradiol (P less than 0.05). The patients' mean height velocity SD score for chronological age, initially 3.8 +/- 1.9, decreased significantly to 0.9 +/- 0.9 with treatment (P less than 0.005). Nocturnal GH secretion (mean GH concentration, sum of GH pulse areas, sum of GH pulse amplitudes, and GH pulse frequency) and mean IGF-I levels (1.38 +/- 0.6 vs. 1.72 +/- 0.34 U/mL) were not significantly altered by treatment. However, the mean peak GH response to GH-releasing factor-(1-44) was 29.2 +/- 6.8 micrograms/L before treatment and declined significantly to 17.7 +/- 3.4 micrograms/L after gonadal suppression (P less than 0.05). PRL secretion was similar before and after GnRH-a-induced suppression. These results indicate that the decrease in height velocity noted during GnRH-a treatment occurred independently of changes in nocturnal GH secretion and IGF-I levels. These data are consistent with the premise that sex steroids can modulate growth by a direct action on skeletal growth.

Antineoplastic Agents

Platelet aggregating IgG antibody to platelet surface glycoproteins associated with thrombosis and thrombocytopenia.

Previously described platelet-aggregating antibodies associated with thrombosis and thrombocytopenia required heparin for their in vivo and in vitro expression. We have observed a patient with thrombosis who became thrombocytopenic during heparin treatment, but who suffered further thrombotic events and continued thrombocytopenia for 3 months after heparin withdrawal. The patient's plasma contained a potent platelet aggregating factor reactive with both his own and normal platelets in the absence of heparin. It also caused [14C]serotonin secretion from labelled platelets from normal donors and patients with either Glanzmann's thrombasthenia or Bernard-Soulier syndrome. This factor was an IgG and was neutralized by antibody specific for IgG lambda light chains. While the patient was thrombocytopenic an IgG paraprotein with lambda light chains was detected by isoelectrofocussing. After corticosteroid treatment it disappeared and the patient recovered. The active, but not the recovery serum contained IgG which immunoprecipitated a glycoprotein with characteristics of Glycoprotein IV from platelets labelled with Na[3H]BH4/periodate. Thus platelet-aggregating IgG antibodies with direct specificity for platelet surface glycoproteins may be associated with thrombosis/thrombocytopenia.

Humans

Persistently raised intraocular pressure following extracapsular cataract extraction.

In this population based study we have reviewed the files of all patients who underwent an extracapsular cataract extraction (ECCE) between 1984 and 1987, were normotensives prior to surgery, and were followed up for at least 10 months after the ECCE. From a total of 1047 operations 746 qualified for the inclusion criteria; of these, 16 (2.1%) were found to have a consistently raised intraocular pressure (greater than 21 mmHg) on more than two occasions) at four months or later after surgery and throughout at least a six-month period. An increased incidence of secondary aphakic glaucoma was associated with anterior chamber IOL implantation (p less than 0.001) and posterior capsule rupture (p less than 0.01), but not with any of the other variables examined (age, sex, surgeon).

Adult

Available FSH receptors in adult rat testis in vivo.

It has been suggested that the tight junctions formed between Sertoli cells during the peripubertal period constitute a barrier to circulating FSH in the adult testis, limiting its access to the lumen of the seminiferous tubules. There are also reports of FSH receptor-binding inhibitors. These observations prompted us to study the extent of FSH receptor availability in vivo in the adult rat. Experimental rats were given an intracardiac injection of rat FSH (rFSH), and the occupied receptor was measured by radioimmunoassay of acid-released rFSH from the testis. In the saline-injected control animals, there were 247 fmol occupied FSH receptors/g testis, and as much as 1788 fmol of the unoccupied high-affinity receptors/g testis, as measured by in-vitro binding studies. After intracardiac injection of increasing amounts of rFSH (up to 606 pmol), receptor occupancy increased to a maximum plateau of only 448 fmol/g testis. In contrast, when rFSH was given by intratesticular injection in order to achieve pharmacological doses in the testis, the maximum binding was 662 fmol/g testis. Scatchard analysis of the in-vivo data revealed, however, that the maximum concentration of the high-affinity receptor was 452 fmol/g testis, a value concordant with the highest in-vivo binding observed in animals given intracardiac rFSH (448 fmol/g). A single injection of the hormone did not induce down-regulation of FSH receptors, regardless of the dose, whereas multiple injections of menotrophin were effective, at least to some extent. Despite the receptor loss, the immediate receptor availability was maintained, suggesting the presence of a receptor pool.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Congenital insensitivity to pain with neuroparalytic keratitis.

Congenital insensitivity to pain is a well-defined entity in the group of sensory deficiency syndromes. To the best of our knowledge, unilateral neuroparalytic keratitis associated with congenital insensitivity to pain has not been reported. We report such a case to alert clinicians to this potentially blinding problem.

Child, Preschool

Differing susceptibilities of platelets from normal individuals and patients with von Willebrand's disease to attack by quinine- and quinidine-dependent antiplatelet antibodies.

Reactivity of quinine- and quinidine-dependent antiplatelet antibodies has been compared in platelet-rich-plasma (PRP) from normal donors and from patients with von Willebrand's disease (vWd). One quinine-dependent antibody (Q.Ab) caused platelet aggregation and [14C] serotonin release with only 7 of 12 normal donors, while another Q.Ab and a quinidine-dependent antibody (Qd.Ab) caused aggregation and release with all 12. Drug-dependent IgG binding and PF 3 availability induced by the antibodies were, however, comparable in all donors. Differences in responsiveness were associated with platelets and not plasma. vWd platelets showed normal drug-dependent IgG binding, but decreased aggregation and serotonin release to most drug-dependent antibodies. Responsiveness was not restored by purified vWf:Ag, but, in one case, was corrected by normal plasma or cryoprecipitate. Drug-dependent binding of the Q.Ab which caused variable responsiveness in normals was to the same platelet antigens (GPIb and GPIIIa) in both normal and vWd platelets and did not require plasma components. Reduced PF 3 availability was seen with some antibodies in some vWd patients. Plasma from two of these patients inhibited aggregation of normal platelets to Q.Ab and one of these inhibited aggregation to ADP. Antiplatelet antibodies were detected in these two plasmas by ELISA. Thus some Q.Ab produce different responses with platelets from different donors. In vWd, reduced responsiveness to Q.Ab and Qd.Ab may result from production of inhibitory antiplatelet antibodies.

Autoantibodies

Circumferential perirenal urinoma mimicking nephromegaly on urography.

Four cases of circumferential perirenal urinoma in patients with cancer are described. Intravenous urography showed evidence of apparent renal enlargement. In 1 case, opacification of extravasated urine was dense enough to be seen on the urogram, and the diagnosis was confirmed by computed tomography (CT). In the other cases, sonography followed by CT diagnosed urinoma, after tumor invasion had been suggested because of the pseudonephromegaly. Ureteral obstruction was demonstrated in all cases, due to retroperitoneal adenopathy in 1 case and to pelvic tumor in the other 3. Sonography or CT is required for the diagnosis of circumferential perirenal urinoma mimicking nephromegaly urographically.

Adult

Plasmodium falciparum: DNA probe diagnosis of malaria in Kenya.

We previously reported isolation of DNA probe which specifically recognizes Plasmodium falciparum and developed a simple method for its use. The sensitivity and specificity of this DNA probe method have now been extensively field tested in comparison with those of conventional microscopic examination of blood films in two separate studies in Malindi, Kenya, involving a total of 1179 patients. In the second study, which used improved techniques, sensitivity of the DNA probe was 89% when compared to microscopy. We conclude that the DNA probe method compares favorably with conventional microscopy in detecting parasite densities as low as 25 parasites per microliter of blood. A significant advantage of the DNA probe method is that it utilizes a standardized procedure which can simultaneously and reproducibly analyze a large number of samples without opportunity for significant reader bias.

Adult

Myofibroblasts in peripheral giant cell granuloma. Light and electron microscopic study.

Myofibroblasts are found in various pathologic conditions including lesions containing giant cells, such as central giant cell granuloma and the giant cell tumor of tendon sheath (nodular tendosynovitis). In the present study, myofibroblasts were found in peripheral giant cell granuloma (PGCG) using the TP-Levanol fast cyanine 5RN histochemical procedure and electron microscopy. A number of myofibroblasts displayed intracellular collagen fibrils. The presence of myofibroblasts supports the reactive nature of PGCG.

Fibroblasts

The clavicle: normal and abnormal.

The clavicle is an unusual long bone with many unique embryologic features. It is often involved in congenital and acquired disorders. Traumatic, inflammatory, neoplastic, metabolic and many other miscellaneous lesions may also affect the bone. Because of its ligamentous attachments and the presence of articulations at both ends, the clavicle can also be involved in arthritic diseases. This article illustrates the radiographic manifestations of many of the disorders of the clavicle that are commonly encountered in clinical practice.

Bone Diseases

The many faces of neuroblastoma.

Neuroblastoma is a common tumor in childhood. It arises in the adrenal gland or in various extraadrenal primary sites of the sympathetic chain. Clinically, it may present as an abdominal mass or as disseminated metastatic disease. We studied 52 patients with neuroblastoma, and the typical and unusual radiographic features of the disease are presented.

Adrenal Gland Neoplasms