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Biomedical subjects

J C Gunnells

Publications and source records attributed to J C Gunnells.

16 recordsLinked to original sources

Parathyroid transplantation: fate of a long-term allograft in man.

Previously our group reported clinical, histological, and biochemical evidence of parathyroid allograft survival in a patient transplanted sequentially with renal and parathyroid tissues from the same donor. After 30 months of function, both grafts were concomitantly rrjected. The prolonged parathyroid allograft survival described in certain experimental animals has been attributed to the tissue's being "immunologically privileged." Our current clinical observations do not support this hypothesis.

Adult

Regulation of function of transplanted parathyroid glands in man.

The results of studies performed in nine patients who had undergone successful parathyroidectomy and gland transplantation are presented. Transplantation of parathyroid tissue to the forearm, performed for therapeutic reasons, provided a unique opportunity to sample parathyroid gland effluent and to assess secretory function in vivo. The relationship of calcium to immunoreactive parathyroid hormone (iPTH) release was studied during calcium and ethylenediamine tetraacetic acid (EDTA) infusions as well as dialysis against a low calcium bath (low calcium dialysis) in patients with chronic renal failure. Calcium infusions caused an abrupt decrease in hormone release down to a persistent base line within 30 minutes, whereas EDTA infusion caused a sharp increase which peaked between 30 to 60 minutes and returned towards base line despite continuation of the hypocalcemic stimulus. Low calcium dialysis caused an irregular release of hormone which appeared to deplete gland reserves during the period of the stimulus. Ready access to the venous effluent of the transplanted tissue makes this an excellent model for studying parathyroid physiology in man.

Calcium

Long-term results with forty-five living related renal allograft recipients genotypically identical for HLA.

During the past decade 45 living related renal allografts have been performed between siblings genotypically identical for HLA. In each case all available family members were serotyped and haplotype analysis was performed. Immunosuppressive therapy consisted of standard azathioprine and prednisone regimens. Only one instance of HLA-D incompatibility was documented. HLA-A, -B haplotypes were identical in each case. Histopathological evaluation by light, immunofluorescence, and electron microscopy was completed. Four patients experienced acute cellular rejection with mild long-term impaired renal function. Five patients had acute cellular rejection but subsequently experienced long-term normal renal function. Twenty-three patients had little or no rejection documented and half of these patients are being maintained without steroid therapy. Five patients had histologically proven acute humoral rejection and, of these, three subsequently lost their allografts whereas two regained relatively normal renal function. Recurrent glomerulonephritis was documented in six cases. One was lobular, one crescentic, and one dense-deposit membranoproliferative glomerulonephritis. Three cases of IgA nephropathy were diagnosed. In each case the recurrent glomerulonephritis reflected the same histopathology and clinical course as the disease realized in the host kidneys. Eighty-seven percent of the 40 surviving patients have been rehabilitated completely and are fully employed.

Follow-Up Studies

Apparent recurrence of progressive systemic sclerosis in a renal allograft.

A young woman with progressive systemic sclerosis (PSS) and renal failure who received a renal transplant from her mother suffered accelerated loss of allograft function in the absence of hyperacute rejection or severe hypertension. A biopsy specimen and pathologic examination of the transplanted organ showed a fluorescent antibody pattern and vascular changes that were indistinguishable from those in the patient's native kidneys. This clinical sequence is a departure from the relative success of renal transplantation in the few previously reported cases of PSS where it has been used as therapy for renal failure.

Acute Disease

Parathyroid autotransplantation in primary parathyroid hyperplasia.

Four patients with primary parathyroid hyperplasia were treated by total parathyroidectomy and autotransplantation of parathyroid tissue into the forearm muscle. All patients remained normocalcemic after vitamin D and oral calcium replacement therapy were stopped at 1 1/2, four, nine and 13 months, respectively. Graft function was documented further by detection of a higher concentration of parathyroid hormone in plasma from the basilic vein draining the graft bed than from the basilic vein in the contralateral arm. Intravenous calcium infusion suppressed parathyroid hormone secretion from the graft whereas hypocalcemia induced by ethylenediaminetetra-acetic acid markedly stimulated hormone release. In two patients histologic examination of a grafted fragment revealed hyperplastic parathyroid tissue. This method of treatment offers a suitable alternative to radical subtotal parathyroidectomy in selected patients with hyperparathyroidism.

Adult

Plasma dopamine-beta-hydroxylase in the diagnosis of neuroblastoma.

An atypical case of neuroblastoma is described, in which the diagnosis was facilitated by the application of a new biochemical procedure, the assay of plasma dopamine-beta-hydroxylase activity. This laboratory tool is proposed as a useful adjunct to established techniques in the diagnosis of neural crest tumors.

Adolescent

Focal glomerular sclerosis: contrasting clinical patterns in children and adults.

In a retrospective clinicopathological study, 48 kidney biopsy specimens from 16 children (mean age, 7 years) and 17 adults (mean age, 33 years) with histological evidence of focal glomerular sclerosis (FGS) were examined using light, immunofluorescence and electron microscopy. The histopathological findings were related to the clinical course of each patient. At the clinical onset of the disease, the nephrotic syndrome was seen more commonly in children (12/16) than adults (7/17), while the incidence of both hypertension (children 1/16 versus adults, 9/17) and renal insufficiency (children, 0/16 versus adults, 7/17) was greater in adults. Despite a shorter average follow-up, (adults 3 10/12 years versus children, 7 years), the incidence of hypertension (adults, 13/17 versus children, 7/16) and renal functional impairment (adults, 13/17 versus children, 3/16) remained greater in the adult patients. One child and three adults died in renal failure while two adults underwent transplantation and on requires regular dialysis therapy. Nine of 15 pediatric patients treated with corticosteroids experienced partial or complete remission in either their nephrotic syndrome or level of urine protein excretion, while just 3 of 6 adult patients treated with corticosteroids experienced a partial remission, but never became protein-free. There was an excellent correlation in all patients between the degree of functional renal impairment and the extent of glomerular and nonglomerular histopathological damage in the kidney. It is concluded that in the adults, FGS represents a more severe and progressive disease process and is less responsive to therapy.

Adolescent

Renal transplantation between HL-A haploidentical donor-recipient pairs: functional and morphological evaluation.

Fifty-nine recipients received renal allografts from an HL-A haploidentical family member. Immunogenicity of the incompatible haplotype was measured by skin grafts exchanged within each family when possible, and renal allograft recipients were assigned prospectively to two groups depending on the skin graft survival time (Group 2A greater than 15 days; Group 2B less than 15 days). If skin grafts could not be accomplished, the patients were place in an unclassified group, Group 2. Renal function at one and 2 years following engraftment did not differ between the two groups. Mixed lymphocyte stimulation of recipient lymphocytes by mitomycin-treated donor lymphocytes also was comparable in the groups. Histopathological evaluation by light, immunofluorescence, and electron microscopy at least 6 months following allografting did not distinguish between the groups. The only differentiating characteristic was that Group 2A patients did not experience their primary rejection episode until an average of 18 days following transplantation, whereas Groups 2B and unclassified 2 had their initial primary rejection episode at average days 9 and 5, respectively. In our clinical program, matching for HL-A halotypes continues to be the best predictor for long-term renal function in consanguineous renal transplantation.

Antibody Formation

Low renin hypertension.

Low renin hypertension comprises a spectrum of disorders ranging from primary aldosteronism to obvious disorders of other mineralocorticoids, as well as a variety of miscellaneous disorders. The largest group of patients with low renin hypertension have no clear abnormality in mineralocorticoid production. However, many lines of evidence suggest the critical role of volume excess in the pathogenesis of hypertension in these patients. More detailed physiological studies must be performed in order to totally understand the spectrum of pathophysiology in low renin hypertension. However, while such studies are in progress the evidence from the literature suggests that these patients must be treated and that in most of these patients diuretic administration, either spironolactone or the thiazide group of diuretics, is usually effective in achieving a reduction of blood pressure to normal.

Adult

Plasma dopamine-beta-hydroxylase activity in oral contraceptive hypertension.

A prospective study was undertaken to evaluate the relative contribution of changes in sympathetic nervous system activity, as reflected by changes in dopamine-beta-hydroxylase (DBH) activity, to the pathogenesis of oral contraceptive-induced hypertension. Precontraceptive and serial post contraceptive determinations of blood pressure, plasma renin activity (PRA), DBH activity, and changes in body weight were obtained in twelve control patients and forty-one oral contraceptive users. Forty-four percent of oral contraceptive users had increases in blood pressure but remained normotensive and 17% became frankly hypertensive. The precontraceptive and average post contraceptive levels of mean arterial pressure (MAP), PRA and DBH activity in each patient were compared using paired group analysis. Control patients (group I) exhibited no significant changes in these variables, while the patients with contraceptive-induced increases in MAP (groups III and IV) underwent significant, parallel increases in DBH activity. Finally, the linear regression of changes in MAP on the percent change in DBH activity was examined. The positive slopes in groups III and IV differed significantly from the negative slope of the controls (group I). The data have been interpreted to reflect an inappropriate oral contraceptive-induced stimulus to sympathetic nervous system activity, leading to increases in MAP in susceptible individuals.

Adult

Fungal infection following renal transplantation.

Twenty-seven deep fungal infections developed in 22 of 171 patients following renal transplantation. These infections included cryptococcosis (ten), nocardiosis (seven), candidiasis (four), aspergillosis (two), phycomycosis (two), chromomycosis (one), and subcutaneous infection with Phialophora gougeroti (one). Twelve infections occurred in living-related and ten in cadaveric recipients. Nineteen of the 22 patients were male. Infections occurred from 0 to 61 months after transplantation. Complicating non-fungal infections were present concomitantly in 15 patients. Thirteen patients died, eight probably as a result of fungal infection. Appropriate diagnostic procedures yielded a diagnosis in 20 of 27 infections, and therapy was begun in 18 patients. Serologic, culture, and biopsy procedures useful in making rapid diagnoses are advocated in the hope of increasing survival.

Adolescent

Transplantation of the parathyroid glands in man: clinical indications and results.

The physiologic function of human parathyroid autografts and allografts has not been demonstrated conclusively. During the past 30 months, we have transplanted parathyroid glands in 29 patients and tested their functional status. One immunosuppressed aparathyroid patient received a parathyroid allograft from a parent who previously had been his renal transplant donor. Twenty-seven patients with renal failure and secondary hyperparathyroidism received parathyroid autografts immediately after total parathyroidectomy, and one patient received a parathyroid autograft at the time of total parathyroidectomy for primary chief cell hyperplasia. At transplantation 1 times 1 mm. parathyroid pieces were grafted into the forearm musculature. Of 11 transplanted patients (one allograft and ten autografts) followed for 1 year, ten are normocalcemic; only two (autografted patients) are on supplemental calcium. Ten of the 29 patients have had biopsies performed, and all have had intact parathyroid architecture and intracellular secretory granules demonstrated by light and electron microscopy. Parathyroid hormone content in the grafted tissue of five patients was 179 plus or minus 118.8 ng. per milligram. In 11 random patients in whom bilateral measurements have been made, the parathyroid hormone content in the antecubital vein blood draining the grafted tissue has been markedly higher than that in the simultaneously sampled antecubital vein blood of the nongrafted arm. These data demonstrate that parathyroid autografts or allografts secret hormone and maintain a normal serum calcium in the host.

Biopsy