Biomedical subjects
Publications and source records attributed to J C Chan.
We wish to draw attention to a case of hypertension in a child with anaphylactoid purpura, but with minimal urinary findings. Early recognition and effective antihypertensive therapy for short periods of time prevent potential complications. The wide spectrum of presentations, the epidemiological features, the diagnostic work-up and the role of the primary care physician are also reviewed.
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We reviewed the neuropathologic characteristics of 52 cases of acquired immune deficiency syndrome (AIDS) at autopsy. Histologically significant neuropathologic lesions were found in 38 cases. We believed that infection was the predominant pathologic process in 26 cases; occasionally, multiple infectious agents were present. This included Toxoplasma encephalitis (n = 16), fungal abscess (n = 1), tuberculous abscess (n = 1), progressive multifocal leukoencephalopathy (n = 2), cysticercosis (n = 1), and Escherichia coli meningoencephalitis (n = 1). Microglial nodules or perivascular inflammation suggested that encephalitis was the most likely cause in five cases. In two additional cases, a primary demyelinating process that was apparently related to cytomegalovirus was present. Vascular or hypoxic diseases were present in nine cases. The findings included intracerebral hemorrhage (n = 1), subarachnoid hemorrhage (n = 2), infarction (n = 2), diffuse hypoxic changes (n = 5), cerebral edema (n = 1), and rare thromboemboli with extravasation of RBCs (n = 1). One case of primary lymphoma was observed. The CNS lesions were the proximate cause of death in 15 patients. The CNS complications of AIDS are varied and often are the major manifestation of the syndrome.
To compare the effects of hydrochlorothiazide (HCTZ) alone and in combination with amiloride on urinary calcium excretion we performed 14 acute studies on 7 patients with vitamin-D-induced calciuria. Each patient was studied first with HCTZ alone, and 1-32 weeks later with the same or lower dose of HCTZ combined with amiloride. Administration of HCTZ alone did not change UCaV during the 1st day of therapy, and caused a significant reduction from 44.4 +/- 28.8 to 26.0 +/- 14.4 mg/m2/24 h (p less than 0.02) on the 4th day. In contrast, combined diuretic regimen caused a significant reduction in UCaV from 36.0 +/- 16.7 to 23.6 +/- 14.4 mg/m2/24 h (p less than 0.02) on the 1st day and further reduction to 13.3 +/- 6.9 mg/m2/24 h (p less than 0.01) on the 4th day. UCaV on the 4th day was significantly lower with the HCTZ-amiloride combination (p less than 0.05). The combined therapy caused a greater reduction in FECa/FENa than HCTZ alone on the 1st day (p less than 0.02) and on the 4th day (p less than 0.01). HCTZ-induced hyperkaluria, hypokalemia and alkalosis were prevented by the addition of amiloride. In another patient, low-dose HCTZ-amiloride had a maximal dissociative effect on FECa/FENa and was more effective than HCTZ given alone in a double dose. 3 patients were treated with the low-dose HCTZ-amiloride regimen for a total of 23 months. UCaV was kept persistently low.(ABSTRACT TRUNCATED AT 250 WORDS)
Two children with X-linked dominant hypophosphatemic rickets treated with vitamin-D metabolites and phosphate supplementation, for prolonged periods, developed hyperparathyroidism with nephrocalcinosis. Calcium infusion tests were performed in both. In one patient, the initial test was done two weeks after all treatment was stopped. Only moderate decrease in the degree of the phosphaturia was recorded. However, a repeat test, performed after all medications were withheld for another four weeks, showed normal anti-phosphaturic response, and she continued to be treated conservatively. In the other patient, the test was done five weeks after withholding treatment. Failure to suppress the phosphaturia provided strong support for the diagnosis of tertiary hyperparathyroidism. He underwent total parathyroidectomy and the parathyroid histology confirmed the diagnosis. In both, control of parathyroid activity stopped the deterioration in kidney function and improved the response of the basic disorder to treatment. It is concluded that in patients with X-linked dominant hypophosphatemic rickets, the calcium infusion test is useful for the differentiation between secondary-reversible and tertiary-irreversible hyperparathyroidism. To avoid continued stimulation of the parathyroid glands by phosphate administration, we recommend that such calcium infusion test be performed and interpreted after at least six weeks have elapsed without phosphate or vitamin-D administration.
Twenty-one (100%) Haitians and 42 (21.5%) of 192 native black Americans autopsied in a 33-month period at Jackson Memorial Hospital, Miami, were included in this review. All autopsied materials were examined. Among the Haitians autopsied, infectious diseases accounted for 11 (52%) of 21 deaths. Toxoplasma encephalitis was the leading cause of death (five cases). Other infectious causes of death included disseminated cryptococcosis (one), disseminated cytomegalovirus diseases (one), Pneumocystis carinii pneumonia (one), chronic active hepatitis B (two), and bacterial pneumonia (one). Malignant neoplasms were also found to be causes of death and these included a single cases of each of the following: adenocarcinoma of the lung, multiple myeloma, diffuse histiocytic lymphoma, hepatoma, and Kaposi's sarcoma. Deaths of the remaining cases were due to hypertensive cardiovascular diseases (two), rheumatic heart disease (one), glomerulonephritis (one), and intimal fibroplasia of coronary arteries (one). Seven Haitian cases fulfilled the Centers for Disease Control case definition for the acquired immune deficiency syndrome (AIDS). For comparison, autopsies of black Americans were chosen from conditions that would most likely predispose them to opportunistic infections. Among the autopsies on black Americans there were no cases of opportunistic infections or Kaposi's sarcoma that were considered to be consistent with the AIDS.
RNA sequence relationships between the genomes of the Kirsten murine sarcoma virus (MSV-K) complex, the Kirsten murine leukemia virus (MuLV-K) complex, the Gross murine leukemia virus (MuLV-G), and the Moloney murine leukemia virus (MuLV-M) were investigated. Sedimentation analyses revealed the expected 30 and 34 S RNA subunits in the MSV-K complex and a previously undetected 30 S RNA subunit accompanying the 34 S RNA subunit in the MuLV-K complex. Nucleic acid hybridization data indicated that each Kirsten virus 30 S RNA subunit had about 40% sequence homology with the RNA genome of MuLV-G, although these sequences were only partially homologous between the two 30 S subunits. In contrast, the MuLV-K 34 S RNA subunit had 96% sequence homology with the MuLV-G genome, whereas the MSV-K 34 S RNA subunit displayed only 71% sequence homology with the MuLV-G genome. Similar relationships were indicated by oligonucleotide fingerprinting. The oligonucleotide data, taken with published sequence data on the MuLV-G and MuLV-M genomes, enabled us to construct partial sequence maps of the MuLV-K 34 S RNA subunit and the MSV-K 34 and 30 S RNA subunits. The sequence arrangements indicated that (1) the MuLV-K 34 S RNA subunit is a variant of the MuLV-G genome; (2) the MSV-K 34 S RNA subunit is a recombinant molecule, which maintains the length of its leukemia virus parent; and (3) the MSV-K 30 S RNA subunit may have been generated from the MuLV-K 34 S genome by a two-stage process, culminating in the retention of parental sequences only within the U5 and U3 noncoding segments and within several amino-terminal coding segments. Further examination of published retrovirus genome sequences revealed several strategically situated sets of potential recognition signals for transcription and translation and suggested a model for genetic recombination based on mRNA splicing signals and areas of limited sequence homology. This model may explain how foreign gene elements can be inserted into retrovirus genomes to generate either functional or defective recombinant retroviruses.
In the past decade major advances in our understanding of renal tubular hydrogen ion secretion and bicarbonate reabsorption have provided new insight into the pathophysiology of renal tubular acidosis. Thus "fragment to fragment clings" and the number of disorders categorized within the syndrome grows, until we have come to know and name four types, with many subtypes. We hope this new perspective provides a basis for the physician to recognize renal tubular acidosis in its several forms so that an informed decision may be arrived at in choosing the best therapy. The physician may also be prepared to reasonably project the prognosis for each patient. We also hope that our detailed examination of renal acidification will provide a reference for delineation of new clinical expressions of acid-base disorders and kidney malfunction certain to be described in the years ahead.
To examine the number of renal biopsies in correlation with the pattern of referrals as well as the major categories of renal diseases for the procedure peculiar to children, the data of 100 consecutive percutaneous renal biopsies using disposable biopsy needles under ultrasound guidance in 99 children were reviewed. To examine the risks and accuracy of the procedure the estimated depth of the kidney by ultrasound, the actual biopsy depth, the success rate and the complications were evaluated. With rare exception, 1 core of renal tissue was obtained per single needle insertion; 109 needle insertions yielded 103 cores. Of the specimens 92 per cent contained more than 10 glomeruli. Gross hematuria with the first voiding post-biopsy occurred in 12 per cent of the cases but persisted beyond 24 hours in only 1 per cent. No long-term complications were observed. Percutaneous renal biopsy with the disposable needle guided by ultrasound represents a considerable advance in diagnostic technique and deserves wider application in the evaluation and management of a number of pediatric kidney disorders.
We evaluated clinical features of five cases of Toxoplasma encephalitis (TE) occurring in recent Haitian entrants into the United States. None of the patients had any underlying malignancy or known immunosuppressive therapy. Histopathologic findings of TE at autopsy were confirmed by peroxidase-antiperoxidase method. Four patients had an antecedent episode of disseminated tuberculosis and all five were receiving antituberculous therapy when neurologic manifestations of lethargy, seizures, and motor weakness first developed. These symptoms progressed into coma and death within 15 days. Peripheral lymphocytopenia was noted in all patients; three were anergic. Parenchymal lesions were identified by CT brain scans and total proteins were elevated in spinal fluid in all cases. TE appears to be a manifestation of the acquired immune deficiency syndrome in Haitians; it should be suspected in those with a febrile illness and multiple focal lesions of the central nervous system.
To delineate the potential role of renal acidosis on zinc and calcium metabolism, 24 male Charles River rats, with a mean weight of 154 g, were assigned to four groups of 6 rats each. Three groups of rats were given ammonium chloride for 5 days by stomach tube at dosages of 4, 8, 16 mEq/kg/day, respectively. The control group received the solvent (normal saline) only. The animals were fed a semi-purified diet containing 100 ppm of zinc. The total food intake averaged 18, 16, 17 and 18 g/day, respectively, for the control and the three treated groups. On the 4th and 5th day, two 24-hour urinary collections for net acid excretion, zinc and calcium excretions were obtained. The net acid excretion progressively increased from 0.85 +/- 0.21 muEq/min/kg in the control rats to maximal values of 10.61 +/- 0.87 muEq/min/kg in the acid-loaded rats. The net acid excretion is highly correlated with the urinary calcium excretion (r = 0.95, p less than 0.01). However, the acid-loading has no effect on the carcass retention of zinc as documented by isotope studies or urinary zinc excretion.
Imparied urinary concentrating ability in Bartter's syndrome may result in part from overproduction of prostaglandins and from the defect in chloride reabsorption by the loop of Henle, or both. To assess the role of prostaglandins, concentration of the urine before and after treatment with prostaglandin inhibitors was studied in 3 patients with this syndrome, taking a constant metabolic diet. Maximal urinary osmolality was determined after overnight fluid deprivation and during infusion of Pitressin. The studies were repeated after 4 days of treatment with the prostaglandin inhibitors, indomethacin and ibuprofen. The maximal urinary osmolality was 694 +/- 39 and 717 +/- 78 mosm/kg, and solute clearance was 1.3 +/- 0.3 and 1.2 +/- 0.5 ml/min for the control and treatment periods, respectively. Prostaglandin inhibitors failed to increase the maximal urinary osmolality or solute clearance. The data thus suggest that factors other than prostaglandin overproduction cause the impairment in urinary concentration in Bartter's syndrome. The defective chloride transport with a loss of interstitial hyperosmolality may be one such factor.
To test the effects of chlorothiazide on vitamin-D2-induced hypercalciuria, we carried out 17 metabolic studies lasting 12 days each in adult Sprague-Dawley male rats. Three groups were studied: (A) control rats receiving only the vitamin-D2 vehicle; (B) vitamin-D2-treated rats receiving 50 IU/day; and (C) rats treated in the same manner as group B with the addition of chlorothiazide 20 mg/day for the last 6 days of the study. Urine was collected during the last 3 days, and a blood sample was obtained at the end of each study period. Analysis of the data showed that there were no significant differences between the groups in changes of serum calcium concentration (A, 6.1 +/- 0.1 mg/dl; B, 6.1 +/- 0.2 mg/dl; C, 6.0 +/- 0.2 mg/dl), serum creatinine concentration (A, 0.5 +/- 0.07 mg/dl; B, 0.52 +/- 0.08 mg/dl; C, 0.48 +/- 0.04 mg/dl), and creatinine clearance (A, 4.8 +/- 0.7 ml/min/kg; B, 5.2 +/- 1.2 ml/min/kg; C, 4.9 +/- 0.5 ml/min/kg). The administration of vitamin-D2 significantly increased the urinary calcium excretion from 6.7 +/- 1.0 mg/kg/day to 19.5 +/- 9.7 mg/kg/day (p less than 0.02), but the calciuria was inhibited in group C rats by the addition of chlorothiazide, which restored urinary calcium excretion to 6.8 +/- 2.5 mg/kg/day (p less than 0.02). Evaluation of the ratio of calcium/creatinine excretion (A, 0.19 +/- 0.03; B, 0.53 +/- 0.25; C, 0.20 +/- 0.07) and calcium/sodium excretion (A, 0.22 +/- 0.05; B, 0.48 +/- 0.25; C, 0.19 +/- 0.04) further confirmed these effects of vitamin-D2 and chlorothiazide on urine calcium excretion. We conclude that in rats conventional doses of vitamin-D2 consistently induce marked hypercalciuria, even without hypercalcemia, and that this hypercalciuria can be effectively prevented by chlorothiazide.
The clinical data, histologic findings, and computed tomographic (CT) abnormalities in eight adult Haitians with toxoplasma encephalitis were analyzed retrospectively. Diagnosis was established by identification of Toxoplasma gondii on autopsy in five and brain biopsy in three specimens and subsequently confirmed by the immunoperoxidase method. All these patients, six of whom had been in the United States for 24 months or less, had severe idiopathic immunodeficiency syndrome. All were lymphopenic and six were on treatment for tuberculosis when the toxoplasma encephalitis developed. All patients were studied with CT when they developed an altered mental status and fever associated with seizures and/or focal neurologic deficits. Scans before treatment showed multiple intraparenchymal lesions in seven and a single lesion in the thalamus in one. Ring and/or nodular enhancement of the lesions was found in six and hypodense areas in two. Progression of abnormalities occurred on serial studies. These CT findings that were best shown on axial and coronal thin-section double-dose contrast studies were useful but not diagnostically pathognomonic. In patients with similar clinical presentation CT is recommended to identify focal areas of involvement and to guide brain biopsy or excision so that prompt medical therapy of this often lethal infection can be instituted.
Historical prospectives of hypertension studies are introduced. The pathophysiology of hypertension, renin-angiotensin-aldosterone system, urea-angiotensin interactions, and essential hypertension are reviewed. The causes of secondary hypertension, especially the renovascular and endocrine causes in the child, neonate and post-transplant patients are discussed. Comments are made on the medical costs of diagnostic work-up. Treatment for hypertension is summarized.
In the normal human body, the extracellular fluid pH of 7.40 is closely protected. Any increase in acidity or alkalinity summons forth three lines of defense, starting immediately with the blood buffers, followed soon by the respiratory system's control of CO2, and finally purged by the renal excretion of the excess acid or base. The complex interrelated processes of the renal responses require a few days to accomplish maximum compensation. We have presented the fundamental principles governing maintenance of the acid-base equilibrium to provide a conceptual framework for understanding the clinical disorders of hydrogen ion metabolism. The somewhat elusive concepts of endogenous acid production and net acid balance have also been reviewed to help reveal the pathophysiology of metabolic acidosis caused by renal tubular acidosis, chronic renal failure, certain infant feedings, and total parenteral nutrition. The development and perpetuation of metabolic alkalosis in relationship to chloride and potassium deficiency have been examined. In the delineation of a clinical acid-base disorder, the clinician must bear in mind the continual interactions of electrolytes and hormonal systems and should be prepared to reevaluate frequently the elected therapy against the changing responses, based on a thorough understanding of physiology. The various types of renal tubular acidosis have manifold facets but the basic understanding of their pathophysiology begins with the concept of the "anion gap," a point of reference that can be used in the differential diagnosis and treatment. In this chapter a number of new causes of type IV renal tubular acidosis--currently considered to be the most common form of renal tubular acidosis--have been pointed out, along with special reference to the mineral, electrolyte, and aldosterone metabolism in the various acidoses and current means of reversing growth failure in the child, especially through bicarbonate treatment. The mechanism of metabolic acidosis in chronic renal failure including metabolic acidosis in children undergoing dialysis and in recipients of kidney transplantation, and its relationships to mineral and electrolyte metabolism have been presented. The pathophysiology of the acidosis related to certain infant formulas and the acidogenic properties of some amino acid solutions employed in total parenteral nutrition have been briefly reviewed. Finally, the metabolic alkalosis seen in a variety of chloride deficiency syndromes, such as Bartter's syndrome and dietary chloride deprivation, has been discussed and a rational approach to evaluation and treatment outlined.
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A child with long-standing steroid resistant minimal-change nephrotic syndrome developed mild muscular weakness. Laboratory studies demonstrated reduction in both protein-bound and ionized calcium concentrations which were accompanied by high serum PTH and low urinary calcium excretion. These findings were related to the marked sustained reduction in the serum concentrations of 25-hydroxyvitamin-D3 and 1,25-dihydroxyvitamin-D3. Relief of the muscular weakness and normalization of serum ionized calcium and PTH were realized with oral administration of 1,25-dihydroxyvitamin-D3 at 0.25 mcg per day. These beneficial effects persisted for over one year of follow-up.