Medicine and Health Sciences Commons^™

Pathophysiology Of Male Hypogonadism Associated With Endogenous Hyperestrogenism — Evidence For Dual Defects In The Gonadal Axis, Johannes D. Veldhuis, James R. Sower, Alan D. Rogol, Frederick A. Klein, Norman Miller, Maria L. Dufau

Surgery Publications

FEMINIZING tumors of the adrenal cortex are associated with symptoms that presumably reflect the combined effects of estrogen excess and androgen deficiency — gynecomastia, diminished libido, attenuated potency, and testicular and prostatic atrophy.1 2 3 4 5 Although such tumors are extremely rare, they provide a unique opportunity to appraise the nature of endogenous estrogen action on the gonadal axis in men. In principle, the pathophysiologic effects of estrogen hypersecretion could be expressed at the level of either the Leydig cell or the hypothalamic–pituitary axis (or both), with consequent suppression of androgen production. In the present studies, we investigated …

Clinical Findings In Four Children With Biotinidase Deficiency Detected Through A Statewide Neonatal Screening Program, Barry Wolf, Gregory S. Heard, Linda G. Jefferson, Virginia K. Proud, Walter E. Nance, Karen A. Weissbecker

Human and Molecular Genetics Publications

Four children with biotinidase deficiency were identified during the first year of a neonatal screening program for this disease in the Commonwealth of Virginia. Two unrelated probands were identified among the 81,243 newborn infants who were screened. In addition, two siblings of one of these infants were found to be affected. Both probands had mild neurologic symptoms at two and four months, respectively, and the two older children had more severe neurologic abnormalities, cutaneous findings, and developmental delay at two and three years of age. However, none of the affected children had acute metabolic decompensation. Previous studies have shown that …

Intraoperative Ceforanide Pharmacokinetics And Protein Binding., Joseph T. Dipiro, Samir M. Bayoumi, Joseph J. Vallner, Robert R. Nesbit, Rajeev Gokhale, J. Peter Rissing

Publications from the Office of the Dean

The pharmacokinetics and protein binding of ceforanide were studied in 15 patients undergoing cholecystectomies. Each patient received ceforanide (20 mg/kg) intravenously on arrival in the operating room, after which serial blood samples were collected during the elimination phase for determination of total and free ceforanide concentrations in the serum. A high-pressure liquid chromatography assay was used, with a centrifugal filtration system for free-drug determinations. Serum concentration data for each individual were subjected to linear regression to determine the elimination rate constants (total and free drug), volumes of distribution, and systemic clearances. The mean elimination rate constants were 0.41 and 0.50 …

Fluorescence Probes For The Study Of Acetylcholine Receptor Function, M. Martinez-Carrion, J.M. Gonzalez-Ros, J.R. Mattingly, J.A. Ferragut, M.C. Farach, D. Donnelly

Biochemistry and Molecular Biology Publications

Our group initiated the use of pyrene derivatives for functional and structural studies of the membrane-bound Acetylcholine Receptor (AcChR) system. Our studies have taken two approaches. We have recently used a hydrophobic derivative (pyrene-l-sulfonyl azide) that is able to bind covalently to regions of the AcChR molecule accessible from the membrane lipid (1) to monitor ligandinduced effects at those hydrophobic regions of the AcChR protein exposed to the membrane matrix (2). The structural effects induced by ligand binding are interpreted in relation to the AcChR "desensitization" process. We have also used a hydrophilic pyrene derivative (1,3,6,8-pyrene tetra sulfonate [PTSA]) to …

Potential And K+ Activity In Skinned Muscle Fibers. Evidence Against A Simple Donnan Equilibrium, R.E. Godt, C.M. Baumgarten

Physiology and Biophysics Publications

ABSTRACT

It has been suggested that potentials measured with conventional microelectrodes in chemically or mechanically skinned muscle fibers arise from a Donnan equilibrium due to myofilament fixed charges. This hypothesis was tested in mechanically skinned frog (Rana pipiens) semitendinosus fibers by measuring the distribution potential (Ed) between fiber and bath with 3 M KCI-filled microelectrodes and the K+ activity gradient (a'K/a) with K+ ion-selective microelectrodes (KISE). If skinned fibers are a Donnan system, Ed should become more positive as pH is decreased, altering the fixed charge on the myofilaments. Consistent with this expectation, Ed was -4.4, -0.6, and +4.8 mV …

Inability To Predict Relapse In Acute Asthma, Robert M. Centor , M.D., Barry Yarbrough , M.D., Judy P. Wood , P.A.

Internal Medicine Publications

No abstract provided.

Cellular Dna Content As A Predictor Of Response To Chemotherapy In Infants With Unresectable Neuroblastoma, A. Thomas Look, F. Ann Hayes, Ruprecht Nitschke, Nancy B. Mcwilliams, Alexander A. Green

VCU Health Publications

We studied the relation between the DNA content of neuroblastoma cells and the response to therapy in 35 infants under one year of age with a diagnosis of neuroblastoma. Using flow cytometric techniques, we found that in 27 cases the primary malignant stem line consisted of neuroblasts with hyperdiploid DNA content, ranging from 1.07 to 2.42 times the finding in normal diploid cells. All remaining cases had diploid stem lines. Diploidy was more common in infants with clinical Stage D neuroblastoma (metastases beyond regional lymph nodes) than in those with other, less advanced stages: 6 of 10 as compared with …

Ventriculostomy-Related Infections, C. Glen Mayhall, Nancy H. Archer, V. Archer Lamb, Alice C. Spadora, Jane W. Baggett, John D. Ward, Raj K. Narayan

VCU Health Publications

We conducted a prospective epidemiologic study of ventriculostomy-related infections (ventriculitis or meningitis) in 172 consecutive neurosurgical patients over a two-year period to determine the incidence, risk factors, and clinical characteristics of the infections. Ventriculitis or meningitis developed in 19 of 172 patients (11 per cent) undergoing a total of 213 ventriculostomies. When data from all these cases plus five cases of nonventriculostomy-related infection were combined, cerebrospinal-fluid pleocytosis was more significantly associated with the diagnosis of ventriculitis or meningitis (P<0.0001) than were fever and leukocytosis (P = 0.07). Risk factors for ventriculostomy-related infections included intracerebral hemorrhage with intraventricular hemorrhage (P = 0.027), neurosurgical operations (P = 0.016), intracranial pressure of 20 mm Hg or more (P = 0.019), ventricular catheterization for more than five days (P = 0.017), and irrigation of the system (P = 0.021). Previous ventriculostomy did not increase the risk of infection with subsequent procedures. We conclude that ventriculostomy-related infections may be prevented by maintenance of a closed drainage system and by early removal of the ventricular catheter. If monitoring is required for more than five days, the catheter should be removed and inserted at a different site. (N Engl J Med 1984; 310:553–9.)

Unidirectional Calcium And Nucleotide Fluxes In Sarcoplasmic Reticulum. I. Interpretation Of Flux Ratios For Different Reaction Schemes, J. J. Feher

Physiology and Biophysics Publications

The relation between unidirectional calcium and nucleotide fluxes was examined for different ATPase reaction schemes of the sarcoplasmic reticulum. The schemes considered differed in the order of sorption and desorption of calcium, ATP, and ADP. The results suggest that the theoretical relation between calcium and nucleotide fluxes depends on the reaction scheme and that experimental measurements can distinguish among them. The results obtained are generally valid and do not depend on assumptions of equilibrium or pseudoequilibrium between intermediate states of the pump.

Undirectional Calcium And Nucleotide Fluxes In Cardiac Sarcoplasmic Reticulum. Ii. Experimental Results, J. J. Feher, F. N. Briggs

Physiology and Biophysics Publications

Unidirectional calcium influx and efflux were evaluated in cardiac sarcoplasmic reticulum (SR) by 45Ca-"0Ca exchange at steady state calcium uptake in the absence of calcium precipitating anions. Calcium efflux was partitioned into a pump-mediated efflux and a parallel passive efflux by separately measuring passive efflux referable to the steady state. Unidirectional and net ATP-ADP fluxes were measured using [3H]-ATP -- ADP and [3H]- ADP -- ATP exchanges. Methods are presented that take into account changing specific activities and sizes of the nucleotide pools during the measurement of nucleotide fluxes. The contribution of competent and incompetent vesicles to the unidirectional and …

Comparison Of Intermediate-Dose Methotrexate With Cranial Irradiation For The Post-Induction Treatment Of Acute Lymphocytic Leukemia In Children, Arnold I. Freeman , M.D., Vivian Weinberg, Martin L. Brecher , M.D., Barbara Jones , M.D., Arvin S. Glicksman , M.D., Lucius F. Sinks , M.D., Marise Weil , M.D., Hansjuerg Pleuss , M.D., Juliet Hananian , M.D., E. Omer Burgert , Jr., M.D., Gerald S. Gilchrist , M.D., Thomas Necheles , M.D., Michael Harris , M.D., Faith Kung , M.D., Richard B. Patterson , M.D., Harold Maurer , M.D., Brigid Leventhal , M.D., Louise Chevalier , M.D., Edwin Forman , M.D., James F. Holland , M.D.

Pediatrics Publications

Abstract

We compared two regimens with respect to their ability to prolong disease-free survival in 506 children and adolescents with acute lymphocytic leukemia. All responders to induction therapy were randomized to treatment with 2400 rad of cranial irradiation plus intrathecal methotrexate or to treatment with intermediate-dose methotrexate plus intrathecal methotrexate, as prophylaxis for involvement of the central nervous system and other "sanctuary" areas. Patients were then treated with a standard maintenance regimen. Complete responders were stratified into either standard-risk or increased-risk groups on the basis of age and white-cell count at presentation.

Among patients with standard risk, hematologic relapses occurred …

Lack Of Influence Of Commonly Used Drugs On Bioassay Indicator Organisms., Joseph T. Dipiro, A. Thomas Taylor, John C. H. Steele Jr.

Publications from the Office of the Dean

Many commonly used pharmaceutical agents have been found to inhibit bacterial growth in vitro. Determinations of antimicrobial concentrations in sera of patients taking nonrecognized antibacterial agents could possibly be altered if bioassay systems are utilized for the determinations. We therefore attempted to determine the in vitro effect of commonly used drugs on bioassay indicator organisms. Fifty-one different agents (antihistamines, anticholinergics, central nervous system agents, cardiovascular agents, analgesics, steroids, muscle blockers, and other miscellaneous agents) were tested for inhibition or enhancement of the growth of Bacillus subtilis, Staphylococcus aureus, Micrococcus luteus, and Klebsiella pneumoniae. None of the agents tested exhibited any …

Treatment Of Inborn Errors Of Urea Synthesis — Activation Of Alternative Pathways Of Waste Nitrogen Synthesis And Excretion, Mark L. Batshaw , M.D., Saul Brusilow , M.D., Lewis Waber , Ph.D., M.D., Wim Blom , Ph.D., Ann Mari Brubakk , M.D., Barbara K. Burton , M.D., Howard M. Cann , M.D., Douglas Kerr , M.D., Peter Mamunes , M.D., Reuben Matalon , M.D., David Myerberg , M.D., Irwin A. Schafer , M.D.

Pediatrics Publications

Abstract

Children with inborn errors of urea synthesis accumulate ammonium and other nitrogenous precursors of urea, leading to episodic coma and a high mortality rate. We used alternative pathways for the excretion of waste nitrogen as substitutes for the defective ureagenic pathways in 26 infants. These pathways involve synthesis and excretion of hippurate after sodium benzoate administration, and of citrulline and argininosuccinate after arginine supplementation.

The children were treated for seven to 62 months; 22 survived. The mean plasma level of ammonium (±S.E.) was 36±2 μmol per liter, and that of benzoate was 1.5±1.0 mg per deciliter. Alternative pathways accounted …

Discordant Expression Of Fetal Hydantoin Syndrome In Heteropaternal Dizygotic Twins, Mary C. Phelan , B.S., John M. Pellock , M.D., Walter E. Nance , M.D., Ph.D.

Human and Molecular Genetics Publications

No abstract provided.

A Cyproheptadine-Reversible Defect In Acth Control Persisting After Removal Of The Pituitary Tumor In Cushing's Disease, Harvey V. Lankford , M.D., H. St. George Tucker , M.D., William G. Blackard , M.D.

Internal Medicine Publications

Abstract

We studied two phases of cortisol feedback suppression of ACTH in nine patients who had had adrenalectomy for Cushing's disease. Four had been treated by adrenalectomy alone and presumably had ACTH-secreting pituitary tumors. Five others were studied two or more years after transsphenoidal removal of an ACTH-secreting microadenoma. In both groups, cortisol-ACTH feedback during the first 30 minutes of cortisol infusion was abnormal; plasma ACTH fell only 2.7±2.6 per cent (mean ±S.E.), as compared with 28.0±10.1 per cent in five hypoadrenal controls (P<0.01). The fall in ACTH during the second phase of cortisol infusion was similar in the patients and the controls. Cyproheptadine corrected the feedback abnormality occurring during the first phase in both groups of patients with Cushing's disease; ACTH fell by 24.4±4.8 per cent (P<0.005). Persistence of a cortisol-ACTH feedback abnormality after removal of the pituitary tumor in Cushing's disease, as well as the correction by cyproheptadine, suggests that higher centers have a role in the pathophysiology of Cushing's disease. (N Engl J Med. 1981; 305:1244–8.)

Traumatic Acute Subdural Hematoma — Major Mortality Reduction In Comatose Patients Treated Within Four Hours, John M. Seelig , M.D., Donald P. Becker , M.D., J. Douglas Miller , M.D., Ph.D., F.R.C.S., F.A.C.S., Richard P. Greenberg , M.D., Ph.D., John D. Ward , M.D., Sung C. Choi , Ph.D

Biostatistics Publications

To discover which factors contributed to recovery after surgical intracranial decompression, we reviewed the records of 82 consecutive comatose patients with traumatic acute subdural hematoma (ASDH) who were treated in a single center under a uniform protocol. The delay from injury to operation was the factor of greatest therapeutic importance. Patients who underwent surgery within the first four hours had a 30 per cent mortality rate, as compared with 90 per cent in those who had surgery after four hours (P

The Location Of Olfactory Receptor Sites. Inferences From Latency Measurements, T. V. Getchell, G. L. Heck, J. A. Desimone, S. Price

Physiology and Biophysics Publications

Excitatory responses recorded from vertebrate olfactory sensory neurons are characterized by long latencies compared with those from other sensory receptors. Explanations which assume free access of the stimuli to receptor molecules presumably located on the olfactory cilia necessarily imply an intrinsic delay in the transduction mechanism. In contrast, the possibility of restricted or delayed access due to diffusion of the stimulus to molecular receptors located on the dendritic knob or proximal portions of the cilia suggests transduction processes having time courses similar to those in other sensory systems. We show that the threshold stimulus concentration and the latency of the …

A Network Thermodynamic Approach To Compartmental Analysis: Na+ Transients In Frog Skin, D. C. Mikulecky, E. G. Huf, S. R. Thomas

Physiology and Biophysics Publications

We introduce a general network thermodynamic method for compartmental analysis which uses a compartmental model of sodium flows through frog skin as an illustrative example (Huf and Howell, 1974a). We use network thermodynamics (Mikulecky et al., 1977b) to formulate the problem, and a circuit simulation program (ASTEC 2, SPICE2, or PCAP) for computation. In this way, the compartment concentrations and net fluxes between compartments are readily obtained for a set of experimental conditions involving a square-wave pulse of labeled sodium at the outer surface of the skin. Qualitative features of the influx at the outer surface correlate very well with …

Early Diagnosis Of Relapse In Acute Myeloblastic Leukemia — Serologic Detection Of Leukemia-Associated Antigens In Human Marrow, Michael A. Baker , M.D., Judith A. Falk , B.Sc., Walter H. Carter , Ph.D., Robert N. Taub , M.D., Ph.D.

Internal Medicine Publications

Abstract

We tested serial bone-marrow samples from 47 adults with acute myeloblastic leukemia in remission for reactivity with heteroantiserums to leukemia-associated antigens, to determine whether imminent relapse could be detected in patients with acute leukemia. Of 26 patients who relapsed by standard morphologic criteria, 21 had increased immunoreactivity of bone marrow for one to six months (mean, 3.7 months) before relapse. High concordance was observed between a positive test and relapse during the period of study (chi-square = 27.53, P

Human Infection From An Unidentified Erythrocyte-Associated Bacterium, Gordon L. Archer , M.D., Philip H. Coleman , D.V.M., Ph.D., Roger M. Cole , M.D., Ph.D., Richard J. Duma , M.D., Ph.D., Charles L. Johnston , Jr., M.D.

Internal Medicine Publications

Abstract

A 49-year-old splenectomized man had an infection from an unidentified, gram-positive, rodshaped bacterium that adhered to the majority of his peripheral-blood erythrocytes. On transmission electron microscopy, the bacterium was seen to be extraerythrocytic and was 0.2 μm wide by 1.0 to 1.7 μm long. It possessed a thick, granular cell wall, a trilamellar membrane external to the cell wall and prominent mesosomes. Attempts to cultivate the organism in vitro or to duplicate the patient's disease in splenectomized animals were unsuccessful. The patient's response suggested that the bacterium was susceptible to cell-wall-active antibiotics and to chloramphenicol but not to tetracycline. …

A Comparison Of Amphotericin B Alone And Combined With Flucytosine In The Treatment Of Cryptoccal Meningitis, John E. Bennett , M.D., William E. Dismukes , M.D., Richard J. Duma , M.D., Gerald Medoff , M.D., Merle A. Sande , M.D., Harry Gallis , M.D., John Leonard , M.D., Branch T. Fields , M.D., Major Bradshaw , M.D., Hubert Haywood , M.D., Zell A. Mcgee , M.D., Thomas R. Cate , M.D., C. Glenn Cobbs , M.D., John F. Warner , M.D., David W. Alling , M.D., Ph.D.

Internal Medicine Publications

Abstract

We compared amphotericin B therapy for cryptococcal meningitis with a newer regimen containing both amphotericin B and flucytosine. In 50 patients with 51 courses of therapy adherent to the protocol, 27 courses were with amphotericin B and 24 with the combination. Even though the combination regimen was given for only six weeks and amphotericin B for 10 weeks, the combination cured or improved more patients (16 vs. 11), produced fewer failures or relapses (three vs. 11), more rapid sterilization of the cerebrospinal fluid (P<0.001) and less nephrotoxicity (P<0.05) than did amphotericin B alone. The number of deaths was the same (five) with each regimen. Adverse reactions to flucytosine occurred in 11 of 34 patients but were not life threatening. We conclude that combined flucytosine-amphoericin B therapy is the regimen of choice in cryptococcal meningitis. (N Engl J Med 301:126–131, 1979)

[Beta]-(2-Hydroxyphenyl)Ethanolamine Hydrochloride [2-Amino-1-(2-Hydroxyphenyl)Ethanol Hydrochloride], Alexandros Makriyannis, James B. Anderson, Joseph T. Dipiro, Edward Kostiner, Gilbert Hite

Publications from the Office of the Dean

CsH~2NO2+.C1 -, m.p. 441-449 K (from ethyl acetate), P212~2 l, a = 7.363 (2), b = 21.824 (6), c = 5.790 (2)/~, Z = 4, D x = 1.354, D m = 1.356 Mg m -3 (flotation: CC14-C6H6). The structure was solved by MULTAN. Full-matrix least-squares refinement converged to R = 0.057 for the R configuration and to R = 0.056 for the S configuration (P < 0.05). This is consistent with spontaneous resolution of the title compound, single crystals of which provided optically active aqueous solutions. A partially occupied oxygen site O(1)' is attributed to the oxidation of the alkyl hydroxyl group to a ketone during the data collection. The CI- is hydrogen bonded to H2(N)554, H3(N)555, and 1-t(O2)655 (2.37, 2-19, and 2.10 A). Both O(1) and 0(2) are internally hydrogen bonded [HI(N)...O(1), 2.41 and H(O1)...O(2) = 2.24 A]. Intramolecular hydrogen bonding may account for the unusual pharmacological properties of this compound in which only the N-C(1)-C(2)-O(1) and the O(1)-C(2)- C(3)-C(4) and O(1)-C(2)-C(3)-C(8) torsion angles (-41, -60, +122 ° ) differ significantly from those of other phenylethanolamines.

A Network Thermodynamic Two-Port Element To Represent The Coupled Flow Of Salt And Current. Improved Alternative For The Equivalent Circuit, D. C. Mikulecky

Physiology and Biophysics Publications

A two-port for coupled salt and current flow is created by using the network thermodynamic approach in the same manner as that for coupled solute and volume flow (Mikulecky et al., 1977b; Mikulecky, 1977). This electrochemical two-port has distinct advantages over the equivalent circuit representation and overcomes difficulties pointed out by Finkelstein and Mauro (1963). The electrochemical two-port is used to produce a schematic diagram of the coupled flows through a tissue. The network is superimposable on the tissue morphology and preserves the physical qualities of the flows and forces in each part of an organized structure (e.g., an epithelium). …

Solid Tumors In Children, Harold M. Maurer , M.D.

Pediatrics Publications

No abstract provided.

Treatment Of Chlordecone (Kepone) Toxicity With Cholestyramine — Results Of A Controlled Clinical Trial, William J. Cohn , M.D., James J. Boylan , M.D., Robert V. Blanke , Ph.D., Marc W. Fariss , B.S., John R. Howell , M.S., Philip S. Guzelian , M.D.

Pathology Publications

Abstract

Industrial workers exposed to the organochlorine pesticide, chlordecone (Kepone), had signs of toxicity in several organs. The extent of toxicity was proportional to the levels of this chemical in the tissues. In 22 patients, chlordecone was eliminated slowly from blood (half time of 165±27 days — mean ± S.E.M.) and fat (half time of 125 days, with a range of 97 to 177), chiefly in the stool. Output of chlordecone in bile was 10 to 20 times greater than in stool, suggesting that chlordecone is reabsorbed in the intestine. Cholestyramine, an anion-exchange resin that binds chlordecone, increased its fecal …

Systemic Membrane Defect In The Proximal Muscular Dystrophies, Nathan A. Pickard , Ph.D., Hanns-Dieter Gruemer , M.D., Harland L. Verrill , Ph.D., Edward R. Isaacs , M.D., Meinhard Robinow , M.D., Walter E. Nance , M.D., Ph.D., Edwin C. Myers , M.D., Barbara Goldsmith , B.S.

Human and Molecular Genetics Publications

Abstract

We studied lymphocyte capping in 61 patients with Duchenne, Becker, limb-girdle, facioscapulohumeral and congenital muscular dystrophies. All showed a markedly diminished percentage of capped cells when compared with 86 normal controls, providing support for previous evidence that an alteration in membrane fluidity may be a common pathogenic feature in several genetically distinct forms of proximal muscular dystrophy.

Heterozygous carriers of Duchenne muscular dystrophy showed diminished capping that was indistinguishable from that of afflicted males and was often present even when serum enzyme levels were normal. Studies in 25 families with 16 suspected sporadic cases indicated that no more than …

Inadequate Parathyroid Response In Acute Pancreatitis, Giles M. Robertson , Jr., M.D., Edward W. Moore , M.D., Donald M. Switz , M.D., Glen W. Sizemore , M.D., Herschel L. Estep , M.D.

Internal Medicine Publications

Abstract

We studied nine consecutive hypocalcemic patients with acute pancreatitis to elucidate the mechanism of hypocalcemia. Mean serum ionized calcium, 0.97 mM, was below the normal mean of 1.16 mM (P < 0.001). Seven of eight patients tested had normal parathyroid hormone levels. All responded to parenteral parathyroid extract by increasing serum ionized calcium and urinary cyclic AMP, indicating parathyroid-hormone-responsive target organs. Calcitonin and glucagon concentrations were increased above normal in some patients, but there was no relation with serum ionized calcium. Parenteral glucagon had no significant effect on serum ionized calcium or calcitonin concentrations. These findings suggest that neither glucagon nor calcitonin was primarily responsible for the hypocalcemia, which did not produce expected increases in serum parathyroid hormone concentrations. Relative parathyroid insufficiency may account for the persistent hypocalcemia frequently observed in patients with acute pancreatitis. (N Engl J Med 294:512–516, 1976)

Hydrodynamic Structure Of Bovine Serum Albumin Determined By Transient Electric Birefringence, A. K. Wright, M. R. Thompson

Physiology and Biophysics Publications

Birefringence relaxation studies on bovine serum albumin (BSA) reveal transient decay described by a double exponential process. The values of the relaxation times lead to estimation of the size of the equivalent ellipsoid of revolution for BSA. Previous measurements of transient birefringence for BSA have shown a single relaxation process, since the apparatus used in obtaining those data was not fast enough to detect the faster relaxation process.