Jose R. Manaligod

Lysosomal glycogen storage disease with normal acid maltase

Two unrelated 16-year-old boys had mental retardation, cardiomegaly, and proximal myopathy. One also had hepatomegaly. Histochemistry and electronmicroscopy of muscle biopsies showed lysosomal glycogen storage resembling acid maltase deficiency. Biochemical studies of skeletal muscle showed increased content of glycogen of normal structure; acid a-glucosidase activity in both urine and muscle was normal. Other enzymes of glycogen metabolism were also normal. The cause of this apparently generalized glycogenosis with no demonstrable enzyme defect is unknown.

Thymoma associated with pancytopenia and hypogammaglobulinemia: Report of a case and review of the literature

Abstract In the patient here described a thymoma, hematopoietic insufficiency, hypogammaglobulinemia and antinuclear antibodies were present. The association of hypogammaglobulinemia and positive antinuclear antibodies with thymoma is cited as evidence of autoimmune disease. The reported cases of thymic tumor and hematopoietic insufficiency are reviewed.

The pathogenesis of hyperchloremic metabolic acidosis associated with kidney transplantation

The mechanism of persistent hyperchloremic metabolic acidosis developing after kidney transplantation was investigated in six patients. In five patients in whom acidosis failed to lower the urine pH below 5.5, an infusion of sodium sulfate also failed to lower the urine pH. Neutral phosphate infusion failed to increase the urine minus blood (U-B) carbon dioxide tension (pCO2) difference normally in these patients. This abnormal response to both maneuvers indicates the presence of a tubular defect for distal hydrogen ion secretion. In the remaining patient, spontaneous acidosis lowered the urine pH below 5.5 and increased the U-B pCO2 normally with the administration of phosphate, demonstrating that this patients distal capacity for hydrogen secretion was intact. The plasma aldosterone level was low in this patient, and thus he had the acidification defect characteristic of aldosterone deficiency. Hyperkalemia developed in two patients; both were aldosterone-deficient, and they had a low fractional potassium excretion ion response to stimulation with sodium sulfate or acetazolamide. In all but one patient, who lost his kidney to accelerated rejection, chronic rejection developed. Homogeneous deposition of complement (C3) along the tubular basement membrane was found in three patients. Our data suggest that a secretory type of distal renal tubular acidosis can be an early sign of the immunologic process that leads to chronic rejection.

Primary cutaneous phaeohyphomycosis: report of seven cases

We report seven cases of primary cutaneous phaeohyphomycosis. There were five males and two females, ranging in age from 42–65 years (mean 57.7 years). Two patients were otherwise healthy, but five were immunocompromised. One patient had rheumatoid arthritis and was on oral prednisone; two were renal transplant recipients, one was a heart transplant recipient, and the fifth had dermatomyositis. No history of trauma was elicited from any of the patients, but in two cases, foreign material was seen in the tissue sections. All lesions were oil the extremities. In two cases, tissues were cultured, and these grew Exophiala jean‐selmei. The others were not cultured because fungal infection was not clinically suspected. No systemic disease developed in any of the cases, and all were cured by the simple, complete excision of the lesions.

Fatal infantile glycogen storage disease Deficiency of phosphofructokinase and phosphorylase b kinase

A girl with congenital limb weakness, mental retardation, and corneal ulceration died with respiratory insufficiency at age 4 years. Histochemistry of muscle biopsy showed only nonspecific myopathy, but electronmicroscopy revealed subsarcolemmal and intramyofibrillar accumulation of glycogen. Biochemical studies showed increased glycogen content of muscle with lack of phosphofructokinase. Phosphorylase b kinase activity was about 30% of normal. The relationship of the double enzyme deficiency to this unusual clinical picture is unclear.

Disseminated strongyloidiasis presenting as purpura

We report a patient with disseminated strongyloidiasis who was being treated with steroids for cerebral edema caused by brain metastases from urinary bladder carcinoma. He had extensive purpura involving the abdomen, arms, and thighs. A skin biopsy specimen showed numerous larvae of Strongyloides stercoralis. Subsequently, rhabdoid larvae of S. stercoralis were isolated in the stool and the sputum. The patient died 2 days later despite thiabendazole therapy.

The pathophysiology of experimental insulin-deficient diabetes in the monkey. Implications for pancreatic transplantation.

In an 11-year study of experimental insulin-deficient diabetes (IDDM) induced in rhesus monkeys by streptozotocin or total pancreatectomy, the authors have found that pathophysiologic changes occur in eye and kidney, which closely resemble the early stages of human insulin deficient diabetes mellitus (IDDM). In addition, morphologic changes of thickening of glomerular capillary basement membrane and expansion of mesangial matrix (by light microscopy) appear within 3 years of onset of hyperglycemia. However, progression to irreversible complications of advanced diabetic nephropathy or proliferative retinopathy, have not occurred. This animal model resembles human disease in that the animals tend to become ketotic unless maintained with exogenous insulin; C-peptide production is low to absent, and large amounts of glycosylated hemoglobin develop within a month of onset. The monkeys differ from humans in the absence of hypertension and hyperlipidemia. The authors suggest that the abnormalities in basement membrane form and function caused by hyperglycemia form the necessary background upon which other factors, such as hypertension and hyperlipidemia, then act to cause irreversible complications. The role of pancreatic transplantation is in prevention of these background changes.Recurrent pulmonary emboli ultimately may produce respiratory insufficiency, severe hypoxemia, and progressive pulmonary hypertension. In many patients this syndrome is silent in its initial phases, and when thrombophlebitis is present it is often unresponsive to anticoagulant therapy. Unless pulmonary embolectomy is undertaken, most of these patients characteristically succumb with severe respiratory insufficiency. Twenty-five patients with this syndrome have been evaluated at the Duke University Medical Center, and 14 were selected for elective pulmonary embolectomy for relief of severe and incapacitating pulmonary insufficiency. In each patient preoperative pulmonary scans and arteriography demonstrated a high degree of vascular occlusion. The obstructing lesions affected both lungs in the majority of patients. Bronchial arteriography was found to be a very valuable method for demonstrating patency of the pulmonary arteries distal to occluding lesions by retrograde filling through collateral vessels joining the bronchial and pulmonary circulations. Preoperatively radionuclide angiocardiography revealed severe right ventricular dysfunction with significantly depressed ejection fractions at rest and during exercise. Retrograde pulmonary arterial flow as shown by selective bronchial arteriography was excellent in ten patients, fair in three, and absent in one. Long term follow-up indicated a clear relationship between the magnitude of arterial backflow at the time of embolectomy and the degree of clinical improvement. There were two perioperative deaths, one from massive reperfusion pulmonary hemorrhage and another from intractable right ventricular failure. Eleven patients with this syndrome were unsuitable candidates for embolectomy and of these, nine had severe distal emboli diffusely spread in the small pulmonary arteries and not amenable to direct removal. One patient had severe right ventricular failure with extreme pulmonary hypertension (145/45 mmHg) and another was massively obese with severe congestive heart failure and expired in the hospital a week later. In this group of 11 patients, three succumbed and most of the others are currently totally debilitated at rest (NYHA Class IV). Long-term follow-up of the surgically managed patients (1 to 15 years) shows that ten patients improved from NYHA functional Class IV to either I or II, another patient from Class III to Class I, and a final patient was only minimally improved.(ABSTRACT TRUNCATED AT 400 WORDS)

Desmoplastic malignant melanoma: a study by conventional and electron microscopy.

A 61-year-old white man presented himself with a mass that had recurred on the chin. Conventional microscopy of sections from this mass showed atypical spindle cells surrounded by abundant collagen and resembled fibrosarcoma. Stains for melanin revealed pigment in the cytoplasms of the atypical spindle cells. Study of sections by electron microscopy demonstrated round, oval, and spindle-shaped cells having desmosomes and containing abundant melanosomes in varying stages of maturation. On the basis of both conventional microscopy and electron microscopy, the diagnosis was desmoplastic malignant melanoma. An unusual finding by electron microscopy was the presence of tubuloreticular intracytoplasmic inclusions in the neoplastic melanocytes.

Inclusion body myositis associated with systemic sarcoidosis.

We report an autopsy study of a 64-year-old female with systemic sarcoidosis. In addition many muscles showed typical light and electron microscopic features of inclusion body myositis. To our knowledge this association has not been previously reported.

Sequential muscle biopsy changes in a case of congenital myopathy.

Muscle biopsies at age 7 months in a set of dizygotic male twins born floppy showed typical features of congenital fiber‐type disproportion (CFTD). One of the twins died at age 1 year due to respiratory complications. The second one subsequently developed facial diplegia and external ophthalmoplegia. He never walked, remained wheelchair bound, and required continuous ventilatory support. He underwent repeat biopsies at ages 2 and 4, which showed many atrophic type 1 muscle fibers containing central nuclei and severe type 2 fiber deficiency compatible with centronuclear myopathy (CNM). Two‐dimensional gel electrophoresis of muscle showed decreases of type II myosin light chains 2 and 3, suggestive of histochemical type I fiber deficiency. The progressive nature of morphological changes in one of our patients cannot be explained by maturational arrest. Repeat biopsies in cases of CFTD with rapid clinical deterioration may very well show CNM.