Richard P. Spencer

Functional Asplenia in Sickle-Cell Anemia

Abstract Observation of Howell—Jolly bodies in the blood of children with sickle-cell anemia suggested the paradox of splenic hypofunction despite clinical splenomegaly. Spleen scans were performed with a sulfur colloid tagged with radioactive technetium (99mTc). No splenic uptake of the colloid was seen in 11 of 12 children with sickle-cell anemia, although many had enlarged spleens. Twenty-five controls, including children with sickle-cell trait and Hgb SC and Hgb S-β thalassemia diseases, regularly demonstrated splenic uptake. Functional asplenia in children with sickle-cell anemia may be a pertinent factor in the susceptibility to infections — particularly pneumococcal infections — that is characteristic of this disease.

The pathogenesis of ischemic gastroenterocolitis of the neonate: Selective gut mucosal ischemia in asphyxiated neonatal piglets

Abstract Necrotizing enterocolitis and intestinal perforation, occurring without distal obstruction of the gastrointestinal tract, are serious lesions of the neonatal period. The onset of gastrointestinal findings is often preceded by severe postnatal stress, usually of cardiorespiratory origin, producing hypoxemia, hypercarbia, and systemic acidosis. Resuscitated infants, usually premature, remain clinically well during a latent period until they develop characteristic signs of enterocolitis, including gastric retention, bile vomitus, abdominal distension and blood streaked, diarrheal stools. Hemorrhagic and necrotic lesions, with or without perforation, are most commonly found in the stomach, ileum, or colon at operation and/or autopsy. The pattern of asphyxia, resuscitation, and a latent period followed by gastrointestinal findings has been the subject of much speculation about the causal relationship of cardiorespiratory distress in infants with necrotizing enterocolitis. The temporal relationship of perinatal asphyxia to the acute onset of gastroenterocolitis is summarized on Fig. 1. An experimental model was designed that simulates conditions of postnatal respiratory distress and allows measurement of intramural and mucosal perfusion to the gut of asphyxiated and resuscitated neonatal piglets, as well as histologic studies of the gut. We suggest that the term “ischemic gastroenterocolitis of the neonate” be adopted to best describe this condition.

Transfusion-Reversible Functional Asplenia in Young Children with Sickle-Cell Anemia

Abstract We recently defined functional asplenia in children with sickle-cell anemia as impaired splenic reticuloendothelial function despite clinical enlargement of the organ. In three children in...

Radiopharmaceuticals for palliation of metastatic osseous lesions: Biologic and physical background

The intimate admixing of bone matrix and bone marrow is a central point in devising therapy of metastatic lesions. Since specific modalities are not yet available for destroying the malignant cells, treatment is usually palliative. The use of stable gallium (Ga-nitrate) and of a diphosphonate (aminohydroxypropylidine diphosphonate disodium) as osteoclast inhibitors is discussed. The marrow, as well as the matrix, can be affected by external radiation. This is also true with bone-seeking radiopharmaceuticals. There is no ideal radiopharmaceutical available for treating metastases in bone, but the characteristics of several presently available (or proposed) are discussed, and possible use of tumor radiation sensitizers or bone marrow protectors is mentioned. Difficulties are also encountered in calculating accurate dosimetry. Clinical experience is needed to determine a reasonable optimal dose with any particular radiopharmaceutical for relief of pain with low bone marrow toxicity.

Incidence and sites of bone lesions detected by 99mTc‐polyphosphate scans in patients with tumors

The value of bone scanning with 99mTc‐polyphosphate was assessed in 186 patients with various types of tumors. The sensitivity of this technique was greater than that of metastatic roentgenographic series and the reported results of 85Srbone scans, in the detection of osseous involvement by tumors. Three cases with normal bone scans and abnormal roentgenographic studies illustrated the necessity and complementary value of comparing bone scan findings with radiographic studies. Patients with carcinoma of the breast, lung, or prostate displayed characteristic patterns of bone involvement by their tumors. The importance of clinical information, including bone symptoms, antecedent bone disease, and serum calcium and alkaline phosphatase, was stressed in the detection and interpretation of bone scan abnormalities.

Aortic Calcification Contributing to Bone Densitometry Measurement

A 75-yr-old glucocorticoid-dependent asthmatic male had a bone mineral density study to assess possible osteoporosis prior to initiating therapy. A radiograph of the lumbar spine revealed an asymmetrical compression of the second lumbar vertebra, marked scoliosis, vertebral osteopenia, and a highly calcified abdominal aorta. Bone mineral density (dual X-ray absolptiometry [DXA]) revealed low bone mass in L2-L4 and a markedly abnonrnal pattern, with a linear central density representing a calcified aorta. Posterior-anterior measurements of the midlumbar region with and without the overlying aorta indicated that the calcified vessel contributed up to 33% of the measured density. This was a far higher contribution than reported in other studies. Lateral DXA measurements of the L2 vertebra and the overlying aorta were performed to validate this finding. The density of the L2 vertebra was 0.215 g/cm(2), and that of the overlying calcified aorta was 0. 210 g/cm(2). This case suggests that aortic calcifications may contribute sign)ficantly to overall lumbar bone density and, unless recognized, can inadvertently lead to misclassification of osteoporosis.

SOME EFFECTS OF ETHANOL ON THE GASTROINTESTINAL TRACT.

Summary1. Alcohol dehydrogenase can be demonstrated not only in rat liver but in the fore and hind stomach and small intestine as well. The specific activity of gastric alcohol dehydrogenase, in crude preparations, is greater than that of the liver enzyme. Alcohol dehydrogenase can be detected in rat and hamster fetal liver. Intestinal alcohol dehydrogenase has a higher specific activity in the first one-third of the gut than in lower regions; some properties of the intestinal enzyme are described.2. A preliminary sampling of human stomach, jejunum, and colon revealed alcohol dehydrogenase in all these tissues.3. No transintestinal accumulative transport was shown by ethanol when placed at the same concentration inside and outside of hamster everted intestinal sacs. However, ethanol was taken up by intestinal segments tested in vitro.4. Addition of 1M ethanol to solutions of 1×10−3M L-proline or glycine resulted in significant depression in intestinal transport of the imino or amino acid, likely due to tissue damage. At ethanol concentrations of 0.1M and lower, there was no significant depression of L-proline or glycine transport.

Extrapulmonary sites of radiogallium accumulation in sarcoidosis

In an effort to detect extrapulmonary sites of radiogallium accumulation in cases of sarcoidosis, 145 separate Ga-67 citrate studies of 114 patients with biopsy-proven sarcoidosis were examined. The most characteristic extrapulmonary radiogallium uptake pattern was the “panda sign” in 47 patients (41%). The most common site of prominent extrapulmonary radiogallium uptake was the lacrimal glands in 101 patients (88%). Second most common was activity in one or more superficial lymph node regions such as the cervical, axillary, femoral, or inguinal in 19 patients (17%). Other extrapulmonary sites included breast uptake in 6 out of 80 women (8%), prominent splenic and nasal uptake in 9 (8%) patients, periportal accumulation in 7 (6%), and cutaneous/subcutaneous activity in 4 (4%). Because many of these individuals were receiving corticosteroids, the natural (untreated) prevalence of extrapulmonary findings may be even higher. Although the sensitivity and specificity of extrapulmonary radiogallium accumulation has still to be determined, many of the sites may be accessible to biopsy both for diagnostic purposes and to follow the effects of medications. It is therefore suggested that whole-body imaging be performed when radiogallium is administered to patients with suspected or known sarcoidosis.

Intestinal transport of cyclic and noncyclic imino acids

Abstract 1. 1. Employing hamster everted intestinal sacs, the transport of l -phenylalanine and l -proline against a concentration gradient had the following indentical characteristics: spatial distribution of transport, inhibition by absence of Na+ from the medium, inhibition by NaCN but not by propionitrile, lack of effect of added ascorbic acid, and the same temperature coefficient (2.3 for a 10° change), In addition, there was mutual inhibition of transport as measured by the equillibrium quantity. These parameters, hence, were unable to provide a distinction between the mechanism of transport of the amino acid and the amino acid (although genetic data suggest that two distinct, but overlapping, transport systems are involved). 2. 2. A series of noncyclic imino acids of the form was also studied for transport against a concentration gradient by the hamster everted small intestine. When X = H, transport occurred with Y = CH 3 , but not when Y = CH 2 CH 3 or larger groupings. Hence, N -methylglycine likely represents the most “sterically bulky” of these compounds to be transported. 3. 3. Cyclic imino acids of the form were transported against a concentration gradient when n = 2 (azetidine-2-carboxylic acid), n = 3 (proline) and n = 4 (pipecolic acid). For n = 1 (aziridine-2-carboxylic acid, lithium salt), the compound did not appear to be transported. Data are presented that cyclic and noncyclic imino acids show cross-inhibition of transport.

The spleen as a hematological organ

The spleen has multiple roles in human physiology. Eitht major functions are discussed in this review (hematopoiesis, erythrocyte destruction, hormonal function in hematopoiesis, culling and pitting, platelet and leukocyte destruction, particulate removal, reservoir function, and immunologic function). Splenic trapping of red cells, and the concepts of hypersplenism, are major responsibilities of this organ. These aspects are placed in perspective for the reader.