Alphabetic sequence decisions for letter pairs with separations of one to three letters.

The alphabet storage and retrieval theory of Klahr, Chase, and Lovelace (1983) was tested for applicability to letter-order decisions. Ss judged whether letter pairs with sequential separations of 1, 2, or 3 letters were in correct or incorrect order. Ss made decisions either in a continuous- or intermittent-attention mode. The results for alphabetic letter-order decisions with a letter separation of 1 were in conformance with the theory of Klahr et al. in both attention modes. However, at letter separations of 2 and 3 letters, Ss made decisions that were more compatible with a symbolic-distance mechanism. Speculation on how Ss could make alphabetic-order decisions in either a memory-consultation or a symbolic-distance manner is made.


Immunocytochemical detection of the growth-associated protein B-50 by newly characterized monoclonal antibodies in human brain and muscle.

The growth-associated protein B-50 also termed GAP-43, F1, pp46, P-57 and neuromodulin is a nervous tissue-specific protein kinase C (PKC) substrate that is considered to play a major role in neurite formation, regeneration, and neuroplasticity. We describe the isolation of seven mouse monoclonal antibodies (Mabs) directed against B-50. The Mabs are produced against the bovine B-50, selected by ELISA for cross-reactivity with its human counterpart, and evaluated on Western blots in comparison with the well-characterized affinity-purified rabbit polyclonal antibodies to rat-B-50. The Western blots show that the Mabs NM1, NM4, and NM6 recognize specifically the B-50 of bovine, human, and rat brain extract and the purified PKC phosphorylated and unphosphorylated rat B-50 isoforms. The Mabs NM2 and NM3 cross-react with bovine B-50 immunoreactive c-kinase substrate (BICKS), a protein sharing a 17 amino acid sequence homology with B-50. Two Mabs are useful for the detection of B-50 immunoreactivity in formalin-fixed human and rat brain tissues. In human specimen of the hippocampus, a characteristic neuropil distribution of B-50 is detected by the Mabs. In human muscle, Mabs reveal B-50 in nerve bundles and in axons at motor end plates. Thus, these Mabs are useful in investigating the function and localization of the B-50 protein.


Kynurenic acid concentrations are reduced in Huntington's disease cerebral cortex.

Huntington's disease (HD) is characterized by gradually evolving selective neuronal death. Several lines of evidence suggest that an excitotoxic mechanism may play a role. Tryptophan metabolism leads to production of quinolinic acid, an N-methyl-D-aspartate (NMDA) receptor agonist, and to kynurenic acid, an antagonist at these same receptors. We recently found increased kynurenine to kynurenic acid ratios in HD postmortem putamen and decreased kynurenic acid concentrations in cerebrospinal fluid, consistent with decreased formation of kynurenic acid in HD brain. In the present study we used HPLC with 16 sensor coulometric electrochemical detection to measure kynurenic acid and 18 other electrochemically active compounds in 6 cortical regions, caudate and cerebellum from controls, HD, Alzheimer's disease (AD), and Parkinson's disease (PD) patients. Significant reductions in kynurenic acid concentrations were found in 5 of 6 cortical regions examined. Smaller reductions of kynurenic acid in the caudate, cerebellum and frontal pole were not significant. No significant reductions were found in the AD and PD patients. Both uric acid and glutathionine were significantly reduced in several regions of HD cerebral cortex, which could signify abnormal energy metabolism in HD. Since kynurenic acid is an antagonist of excitatory amino acid receptors, a deficiency could contribute to the pathogenesis of neuronal degeneration in HD.


Presence of dopamine D1 receptors and absence of dopamine D2 receptors in human cerebral meningioma tissue.

Preliminary studies have shown that the dopamine D1 receptor is expressed in cerebral meningioma tissue. The current study presents evidence that the iodinated dopamine D1 antagonist [125I]SCH-23982 bound to dopamine binding sites in 33 of the 45 human cerebral meningiomas examined for this. Saturation curves and the linearity of the Scatchard analysis indicate that [125]SCH-23982 binds to a homogeneous population of binding sites. Competition curves reveal the presence of a dopamine D1 receptor by rank order of various dopaminergic and nondopaminergic antagonists ((+)-SCH-23390 greater than (+/-)-SKF-83566 greater than (cis)-flupentixol greater than (+)-butaclamol greater than chlorpromazine greater than 1-sulpiride greater than mianserin greater than (-)-butaclamol). Stereoselectivity was evaluated by (+)- and (-)-butaclamol. The mean (+/- standard deviation) dissociation rate constant was 369 +/- 196 pM with a density of 31.9 +/- 12.5 fmol/mg membrane protein among 33 meningiomas. The dopamine D2 receptor was not present in the 30 meningiomas examined for this. These findings indicate that the dopamine D1 receptor identified is expressed alone and is therefore regulated independent of a D2 receptor in cerebral meningioma tissue. Although the function of the dopamine D1 receptor in cerebral meningiomas has not so far been defined, previous studies have suggested that the D1 receptor might be involved in the control of proliferative growth of meningiomatous tissue.


Dextromethorphan and high-dose benzoate therapy for nonketotic hyperglycinemia in an infant.

To test the hypothesis that nonketotic hyperglycinemia causes overstimulation of the excitatory N-methyl-D-aspartate receptor by allosteric glycine activation, and that reduction of glycine and blocking of the cation channel coupled to the receptor would be beneficial, we administered benzoate and dextromethorphan, a blocker of the N-methyl-D-aspartate channel to an infant with nonketotic hyperglycinemia. Therapy with benzoate, 500 mg/kg per day, was started on day 5, and the dosage was increased to 750 mg/kg per day on day 8, with prompt normalization of the neurologic and electroencephalographic findings. The glycine concentrations in both plasma and cerebrospinal fluid were substantially reduced. Dextromethorphan was added to the regimen on day 12. The electroencephalogram remained normal until the infant was 8 months of age, when diffuse slowing became apparent. Serial brain magnetic resonance imaging showed delayed myelination. At 12 months of age, physical examination findings and growth were normal except for hypotonia. The developmental quotient was approximately 60, and the child was free of seizures. This outcome, although not ideal, is better than that typical for nonketotic hyperglycinemia. Our results suggest that trials with additional patients and other N-methyl-D-aspartate cation channel blockers are warranted.


Tissue-specific mosaicism for trisomy 21 and congenital heart disease.

Cytogenetic studies in a girl with ventricular septal defect and mosaicism for trisomy 21 showed that trisomy was present in most cells from the myocardium and lung but in only a minority from the skin and lymphocytes. These findings emphasize the importance of tissue-specific mosaicism as a cause of certain cardiovascular diseases.


Association between increased atrial natriuretic peptide and reduced cisplatin nephrotoxicity in rats.

Plasma atrial natriuretic peptide (ANP) concentrations were monitored in two experimental models of protection from cisplatin nephrotoxicity. Sprague-Dawley rats made diabetic with streptozotocin (65 mg/kg) were protected from cisplatin-induced nephrotoxicity when compared to control rats as indicated by reduced plasma creatinine (0.49 +/- 0.02 vs. 0.9 +/- 0.06 mg/dl; P less than .001) and blood urea nitrogen concentrations (18.51 +/- 1.4 vs. 43.08 +/- 2.1 mg/dl; P less than .001). Plasma ANP was also increased with experimental diabetes (76.5 +/- 8.98 fmol/ml) vs. normoglycemic controls (43.8 +/- 8.9 fmol/ml; P less than .02). When diabetic rats were treated with insulin, the renal protection observed with the diabetic state was reversed (creatinine, 0.70 +/- .05 mg/dl); plasma ANP concentrations were also reduced (52.2 +/- 15.2 fmol/ml). Renal platinum concentrations were significantly lower in the diabetic group and the reversal of diabetic-induced renal protection with insulin was associated with increased renal platinum concentrations. In rats given a single i.p. dose of cisplatin (5 mg/kg), a reduction in cisplatin-induced nephrotoxicity was observed when 5% NaCl was the vehicle of choice compared to that seen in rats given the same dose of drug in 0.9% saline (creatinine, 0.43 +/- 0.07 with 5% NaCl vs. 0.63 +/- 0.03 with 0.09% NaCl). NaCl (5%) administration also resulted in increased plasma ANP concentrations when compared to rats receiving equivalent volumes of 0.9% NaCl (88.4 +/- 6.2 vs. 50.5 +/- 5.6 fmol/ml, respectively). These data suggest that increased endogenous ANP may be a mechanism of renal protection common to both experimental diabetes and hypertonic saline administration. Chronically increased ANP may prevent renal accumulation of platinum in the kidney.


Postural changes in dental hygienists. Four-year longitudinal study.

Numerous surveys identify the occurrence of musculoskeletal complaints as a concern in dentistry. However, no longitudinal data exist to indicate whether postural changes occur as a result of practicing dental hygiene. The purpose of this preliminary, four-year longitudinal study was to investigate whether any postural changes developed during the hygienists' clinical education and/or during subsequent dental hygiene practice after one and/or two years. It was anticipated that the awkward positions and intense physical demands placed on hygienists might initiate musculoskeletal problems, but that no postural changes would occur over this short period of time. Nine of 10 dental hygienists in the graduating class of 1987 were surveyed for existing musculoskeletal complaints, and the subjects were photographed for a measurement of postural change. Responses from participants indicated an increase in musculoskeletal-related complaints in each of the six areas investigated. The photographic findings indicated that one of the nine hygienists showed an increase in forward head posture, a postural change.


Potentiation of brain natriuretic peptides by SQ 28,603, an inhibitor of neutral endopeptidase 3.4.24.11, in monkeys and rats.

The depressor, natriuretic and cyclic GMP responses to several species of brain natriuretic peptide (BNP) were compared to atrial natriuretic peptide (ANP) 99-126 in conscious spontaneously hypertensive rats (SHR) and in conscious cynomolgus monkeys treated with vehicle or the selective neutral endopeptidase (NEP 3.4.24.11) inhibitor N-[2-(mercaptomethyl)-1-oxo-3-phenylpropyl]-beta- alanine (SQ 28,603). In the conscious SHR, the natriuretic and cyclic GMP responses to 3 nmol/kg i.v. rat BNP-32 greater than rat ANP 99-126 greater than pig BNP-26 and were significantly potentiated by 100 mumol/kg i.v. SQ 28,603. Human BNP-32 was inactive in the SHR treated with either vehicle or SQ 28,603. In contrast, 1 nmol/kg i.v. of human BNP-32 stimulated renal and depressor responses in the conscious monkeys that were greater than or equal to those elicited by human ANP 99-126, whereas 3 nmol/kg i.v. rat BNP-32 reduced mean arterial pressure without affecting renal function. Furthermore, SQ 28,603 (100 mumol/kg, i.v.) significantly enhanced the cumulative losses of sodium and cyclic GMP stimulated by each of these peptides. In conclusion, the renal and depressor activities of BNP are highly species specific and are significantly potentiated by an inhibitor of NEP 3.4.24.11 in conscious SHR and monkeys. Therefore, protection of endogenous BNP may contribute importantly to the activity of NEP 3.4.24.11 inhibitors in cardiorenal disorders such as hypertension and congestive heart failure.


The iron uptake mechanisms of enteropathogenic Escherichia coli: the use of haem and haemoglobin during growth in an iron-limited environment.

The iron uptake mechanisms of enteropathogenic Escherichia coli (EPEC) were examined and compared with those of control E. coli strains. The incidence of aerobactin production was similar (39% and 37% respectively) in the two groups. The quantities of enterochelin produced by aerobactin-negative EPEC and control strains were similar, as were the quantities of enterochelin produced by aerobactin-positive EPEC and control strains. The ability to use haem or haemoglobin as an iron source in an iron-restricted environment was found in 80.4% and 60.8% of EPEC strains respectively, and in 76.6% and 56.6% of control E. coli strains. The ability of E. coli strains to use these compounds was not related to the production of enterochelin or aerobactin or to the production of haemolysins, and may be an important characteristic of bowel organisms. When growing in an iron-limited environment, the iron contained in haemoglobin was used in preference to ovotransferrin-bound iron. During periods of haemoglobin-stimulated growth, the enterochelin uptake system was shown to be fully expressed and may be involved in transport of haemoglobin-derived iron into the cell. Uptake of ovotransferrin-bound iron took place immediately upon exhaustion of haemoglobin-derived iron. The ability to use iron derived from haem compounds represents an alternative iron uptake mechanism for organisms growing in an iron-limited environment and allows greater flexibility during growth in vivo.


Regulation of the nucleotide dependence of the cardiac sarcolemma Ca(2+)-ATPase.

The nucleotide dependence of the Ca(2+)-ATPase purified from cardiac sarcolemma by calmodulin-affinity chromatography was investigated for preparations either in the basal state or activated by three procedures: (i) addition of calmodulin; (ii) addition of phosphatidylserine and (iii) controlled proteolysis. Upon activation, the maximal velocity of ATP hydrolysis increases by a factor of 4-5, while the curves of ATP dependence of ATP hydrolysis change from hyperbolic to biphasic, revealing the presence of two Kmapp for ATP. A tight coupling between Ca2+ and ATP binding sites was also observed. At high ATP concentration, the ATPase activity of the basal state shows a complex dependence on Ca2+ concentration, increasing sharply at millimolar Ca2+. Our results indicate that this increase in ATPase activity is paralleled by the appearance of a second, low affinity Kmapp for ATP. When only the high affinity site for ATP is occupied the ATPase activity of the basal state displays a simple, hyperbolic dependence on the Ca2+ concentration. In addition, increasing Ca2+ concentration appears to decrease the ATP binding at the low affinity site of the enzyme. The effect of ADP on ATP hydrolysis was also examined. The finding that ADP is a potent inhibitor of the purified Ca(2+)-ATPase from heart suggests that the stimulatory action of ADP observed in cardiac sarcolemmal vesicles is not an intrinsic property of the enzyme.


[Atrial natriuretic peptide and plasma renin activity in patients with stable chronic obstructive pulmonary disease].

The relationship between plasma atrial natriuretic peptide (ANP) and plasma renin activity (PRA) was examined in patients with stable chronic obstructive pulmonary disease (COPD, n = 17). The plasma ANP level in patients was approximately twice that in normal subjects. A reciprocal relationship between ANP and PRA was shown in normal subjects; however, this relationship was not observed in COPD. Plasma ANP levels inversely correlated with PaO2, and tended to inversely correlate with angiotensin converting enzyme activity in serum. These results demonstrate that patients with COPD have higher plasma ANP concentration, and that ANP and PRA are not reciprocally related in stable COPD.


Postcesarean endometritis: a brief review and comparison of three antibiotic regimens.

Three different antibiotic regimens (trospectomycin plus azteonam, clindamycin plus azteonam, and triple antibiotics-ampicillin plus clindamycin plus gentamicin) were all effective in treating patients with postcesarean endometritis. Patients are frequently cured clinically despite the fact that the offending organisms may be isolated in post-treatment cultures. Treatment of postcesarean endometritis without obtaining endometrial cultures is acceptable gynecologic practice. Obtaining post-treatment cultures is clearly not cost effective nor clinically beneficial. Drug treatment efficacy should be evaluated by clinical response. This communication is the first to report the new antibiotic, trospectomycin, in the treatment of postcesarean endometritis. Further clinical trials are currently underway.


Rare point mutation at codon 301 and 969 of FMS/M-CSF receptor in acute myelomonocytic and monocytic leukemia.

We have investigated whether point mutations occurred at codon 301 or 969 of FMS (M-CSF receptor) in 19 patients with acute myelomonocytic (M4) and monocytic leukemia (M5). Nineteen peripheral blood and bone marrow blood samples collected from M4 and M5 patients were examined by using polymerase chain reaction and hybridization to allele specific oligonucleotide probes. Mutations at codon 301 and 969 of FMS were not detected in any samples. FMS gene mutations at codon 301 and 969 were rarely involved in M4 and M5 patients in Japan.


Pediatric leukemia/lymphoma with t(8;14)(q24;q11).

A variety of chromosomal translocations occur in pediatric T-cell acute lymphoblastic leukemia (T-ALL) in which a cellular oncogene or growth-related gene is translocated to the alpha/delta locus of the T-cell receptor gene. The t(8;14)(q24;q11) has been described at the cytogenetic and molecular level, but the disease associated with this translocation has not been defined clinically. Fifteen pediatric cases of leukemia/lymphoma with a t(8;14)(q24;q11) chromosomal translocation were collected from previous publications and institutional records. The estimated prevalence of this abnormality among all cases of ALL was 1%. The t(8;14)(q24;q11) disease was characterized by male predominance (10/15), a median age of 5.5 years (range 1.8-17 years), high white blood cell count (median 95 x 10(9)/l), central nervous system infiltration (4/11), bulky extramedullary leukemia (10/11), and T-cell immunophenotype (12/15). The median event-free survival was 4 months, and the median survival, 11 months. Seven cell lines with t(8;14)(q24;q11) were established from six of the cases; four were T-lymphoblastic, one was T-lymphoblastic, but expressed myeloid-related antigens, and two were predominantly myeloid. t(8;14)(q24;q11) leukemia/lymphoma and other ALLs involving 13(q11) have in common a high tumor burden, early spread to extramedullary sites, a propensity to form T-lymphoblastic or T-myeloid cell lines and, usually, an aggressive clinical course.


Expression of M-CSF and its receptor (C-FMS) during factor-independent cell line evolution from hematopoietic progenitor cells cocultivated with gamma irradiated marrow stromal cell lines.

Gamma irradiation of plateau-phase clonal bone marrow stromal cell lines produces factor-independent growth of cocultivated clonal interleukin-3/granulocyte-macrophage colony-stimulating factor-dependent hematopoietic progenitor cell lines. The process is associated with three biologic changes including: (i) adherence of hematopoietic cells to stromal cells forming 'cobblestone islands'; (ii) an intermediate stage [during which the cells show proliferation in suspension in the presence in leukemogenic stromal factor (LSF), a factor similar to macrophage colony-stimulating factor (M-CSF) released by irradiated stromal cells, and transient hematopoietic cell surface expression of MAC-1, and c-fms (M-CSF receptor)]; and (iii) a third stage of factor-independence. A monoclonal antibody to M-CSF receptor inhibited proliferation of intermediate stage but not all factor-independent cell subclones. In the present studies, a subclonal factor-independent malignant subline of FDC-P1JL26 derived by cocultivation with gamma-irradiated stromal cells as well as the parent clone and intermediate stage cells were shown to express significant levels of M-CSF polyA+ mRNA and M-CSF of at least two sizes (23 and 15 kDa) as detected by 35S-methionine labelling and immunoprecipitation with polyclonal anti-M-CSF antiserum. There was no significant difference in intracellular M-CSF protein size between cells at each of the three stages of biologic change. This M-CSF was not detected on the cell surface by fluorescence-activated cell sorting (FACS). In contrast, c-fms expression at the cell surface was detected by FACS analysis and c-fms polyA+ mRNA was only detected during the intermediate stage of induction of factor-independence. FDC-P1JL26 parent cells, the subclone stimulated by LSF, and the factor-independent subclone, showed little or no detectable autophosphorylation of the c-fms receptor at tyrosine. There was no detectable rearrangement of the M-CSF or c-fms genes by Southern analysis between clonal lines during the three stages. While we cannot rule out an autocrine mechanism or mutated c-fms receptor mechanism, the data also suggest that evolution of hemopoietic cell factor-independence during cocultivation with irradiated stromal cells may involve a mechanism distal to the c-fms receptor/M-CSF interaction.


Effects of losartan, a nonpeptide angiotensin II receptor antagonist, on cardiac hypertrophy and the tissue angiotensin II content in spontaneously hypertensive rats.

Losartan, a recently developed nonpeptide angiotensin II (Ang II) receptor antagonist, was administered orally to 10-week-old spontaneously hypertensive rats (SHR) for 2 weeks. Cardiac weight and tissue Ang II, as well as plasma renin activity (PRA) and Ang II, were determined. Treatment with Losartan (10 mg/kg per day) lowered blood pressure markedly. Losartan reduced significantly the left ventricular weight by 11% compared with control rats. The left ventricular Ang II content was lowered by Losartan (18.6 +/- 0.9 pg/tissue; 21.9 +/- 0.9 pg/tissue, control, p less than 0.05), whereas PRA and plasma Ang II concentration were increased by the treatment. With the control and Losartan-treated animals, there was a significant positive correlation between the left ventricular weight and the tissue Ang II content (r = 0.563, p less than 0.05). These results provide evidence that cardiac tissue Ang II, rather than circulating Ang II, plays an important role in the pathophysiology of left ventricular hypertrophy of this animal model of human hypertension.


Impairment of contractile response to carbachol and muscarinic receptor coupling in gastric antral smooth muscle cells isolated from diabetic streptozotocin-treated rats and db/db mice.

This work explored the role of the cholinergic pathway, assessed at a post-synaptic level by the use of isolated smooth muscle cells, in the impairment of antral motility associated with diabetic gastroparesis. Contractile response to carbachol--but not to erythromycin, a motilin receptor agonist--was abolished in antral smooth muscle cells isolated from (i) rats previously rendered diabetic by a single i.v. dose of streptozotocin (STZ, 60 mg/kg) and (ii) db/db spontaneously diabetic mice. Insulin treatment of STZ-rats was able to prevent the impairment of the carbachol contractile response, but not to reverse it once established. In STZ-rats, impairment of contractile response was not associated with a change in density of [3H]-N-methyl-scopolamine ([3H]-NMS) binding sites (approximately 1.5 fmol/mg protein). Displacement curve of the [3H]-NMS binding by carbachol was shifted to the right in diabetic rats as compared to controls. The addition of GTP-gamma-S induced a shift to the right of the displacement curve in control but not in diabetic animals. These results strongly suggest that diabetes is associated with an early and specific alteration of the muscarinic control of contraction of antral smooth muscles at a post-synaptic level, associated with an alteration of the GTP-binding proteins coupled to muscarinic receptors.


Effect of local injection of 8-OH-DPAT into the dorsal or median raphe nuclei on extracellular levels of serotonin in serotonergic projection areas in the rat brain.

Using in vivo microdialysis, we have examined the effects of local administration of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) into either the dorsal (DRN) or the median (MRN) raphe nucleus on extracellular levels of serotonin (5-HT) in the corresponding projection fields, namely striatum and ventral hippocampus in the anaesthetized rat. Local injection of 8-OH-DPAT (0.5 microgram/0.1 microliter) in the DRN reduced extracellular 5-HT levels in the striatum (-55%) and to a lesser extent in the hippocampus (-22%). When injected at the same dose in the MRN, 8-OH-DPAT caused a marked decrease in 5-HT output in the hippocampus (-41%) and had no effect in the striatum. Autoradiographic studies performed on brains from animals that received a local injection of [8H]8-OH-DPAT into either the DRN or MRN under similar experimental conditions indicated that the radioactivity remained localized within each midbrain raphe nucleus. These results confirm anatomical data demonstrating that the striatum and the ventral hippocampus receive their serotonergic innervation preferentially from the DRN and the MRN, respectively.


B-50/GAP43 localization on membranes of putative transport vesicles in the cell body, neurites and growth cones of cultured hippocampal neurons.

We conducted an electron microscopic immunocytochemical study to locate B-50/GAP43 in various cellular elements of hippocampal neurons grown in dissociated cell culture. B-50 was detected with pre- and post-embedding immunoincubation, using affinity-purified B-50 antibodies and secondary antibodies coated on gold probes. For the first time ultrastructural evidence is presented for the location of B-50 on the membranes of electron-lucent transport vesicles with a diameter of 99.4 +/- 2.9 nm, present in the trans region of the Golgi apparatus, in neurites and in growth cones of cultured hippocampal neurons.


Larvicidal properties of macrophages induced by cloned murine schistosomal egg antigen-specific CD4 positive T-helper lymphocytes.

The role of T-helper (TH) lymphocytes in activating peritoneal macrophages (PM) to kill larvae of the helminth Schistosoma mansoni (schistosomula) was investigated with the use of egg antigen-specific CD4 positive TH clones of both the TH1 and TH2 types. Results showed that stimulated TH1 clones, in exceedingly small numbers, or supernatants thereof, conferred on PM the ability to kill schistosomula. The molecule responsible for PM activation was found to be interferon-gamma (IFN-gamma). IFN-gamma-induced PM larvicidal activity was dependent on live cells, energy, as well as protein synthesis, and appeared to be mediated by toxic nitrogen metabolites. In contrast, egg antigen-specific TH2 clones, or their supernants, failed to induce PM larval killing, as they did not secrete IFN-gamma, or any equivalent macrophage activating factor. We postulate a mechanism by which egg antigen-specific TH1 clones may be capable of playing a critical role in the resistance to schistosomal reinfection through IFN-gamma-mediated activation of macrophage helminthotoxicity.


Issues and epidemiological evidence regarding radiation-induced thyroid cancer.

The available information on the induction of thyroid cancer in humans by ionizing radiation is summarized and weaknesses or gaps in assessing risk are identified. Issues to be addressed include: average estimates of thyroid cancer risk from external irradiation, the effects of age on thyroid cancer induction, shape of the dose-response curve for acute irradiation, magnitude of risk at low doses, effects of dose fractionation or dose protraction, the relative effectiveness of iodine-131 (131I) in inducing thyroid cancer compared to external radiation, the temporal course of radiogenic thyroid cancer risk, mortality caused by thyroid cancer, host-susceptibility factors for radiogenic thyroid cancer, and biological factors in risk. It is concluded that the most important needs are to obtain more information on thyroid cancer risks following low-level or highly fractionated radiation exposures and following 131I exposure in children.


[The diagnostic use of laparoscopy in liver pathology in light of the evolution of imaging diagnosis].

We considered 87 patients suffering from chronic hepatic pathology. 62 patients have resulted suffering from cirrhosis or chronic active hepatitis, 25 from neoplasias. In the patient's group with chronic liver disease the humoral tests were not able to differentiate between cirrhosis or chronic active hepatitis. In the present retrospective experience echography showed sensibility 0.53 and specificity 0.91. In cirrhosis group, sensibility 0.5 and specificity 0.60 in chronic active hepatitis, sensibility 0.8 and specificity 0.95 in the neoplasia group. Peritoneoscopy showed sensibility 0.97 and specificity 0.93 in the cirrhosis group and sensibility 0.90 and specificity 1.00 in the neoplasia group. We had one case of major complication: hemoperitoneum from tear of adhesion secondary to previous laparotomy. We can conclude that peritoneoscopy is an useful procedure in the study of liver chronic disease and it still finds indication in selected cases of focal illness.


Binding of human alpha-interferon in the brain tissue membranes of rat.

The receptor binding characteristics of human lymphoblastoid alpha-interferon (IFN) to human Daudi cell line was compared with its binding to membrane homogenates derived from various regions of rat brain. Rat brain membranes bound specifically a detectable amount of I-125 alpha interferon revealing the receptor affinity constant (Kd) of 3.9-4.2 x 10(-10) M and the Bmax was 0.9-1.7 fmoles/mg wet weight tissue depending on the analyzed brain region (the highest Bmax was obtained in the membranes from the hypothalamus region, the lowest one from the spinal cord membranes).


Cholelithiasis associated with medroxyprogesterone acetate therapy in men.

Five out of forty-five adult men, 50 years of age or less, who had received, for at least six months, medroxyprogesterone acetate (MPA, Depo Provera) IM, 200-400 mg/week, for prevention of sex-offending or genital-mutilating behavior developed symptomatic cholelithiasis. Thirty of these men were studied with gallbladder ultrasound prospectively off MPA and at six-month intervals while taking the medication and then six months off MPA. Gallstones recovered from two patients were found to have very high cholesterol content, suggesting they were formed in cholesterol supersaturated bile. These findings are consistent with the increased incidence of gallbladder disease related to high-progesterone states and suggest that MPA may be a causative agent in cholelithiasis. The physiologic studies on gallbladder contraction and cholecystokinin release in a subset of the patients failed to provide information on a mechanism for the possible increased incidence of gallbladder disease.


[Current role of laparoscopy in the diagnosis and treatment of ovarian cysts].

Between October 1986 and March 1990, 220 patients underwent surgical treatment for ovarian cysts. 156 of these patients underwent an initial celioscopy and could potentially benefit from celiosciopic treatment. The group mean age was 33.3 years. The circumstances under which the cysts were discovered usually consisted of pelvic pain or diagnosis during a routine examination. Twenty-four patients underwent laparotomy immediately after coelioscopy either due to a suspect macroscopic diagnosis either due to technical difficulties. 84.6 percent of the patients in the group were able to undergo celioscopic treatment only, essentially consisting of intraperitoneal cystectomy. The main advantages were the reduction in adherent sequelae in these women of a sexually active age, but also some financial savings related to the reduced duration of hospitalization and of sick leave. The theoretical reservations consist of the risk of malignancy and macroscopic diagnosis following coelioscopic exploration must be very restricted, with laparotomy whenever there is any doubt. No malignant tumor was escaped detection in this group.


Changes in the expression of the tumor-associated antigen recognized by monoclonal antibody 44-3A6 in A549 cells due to calcium.

Although there is extensive data available on Ca2+ effects in normal tissues, comparatively little is known about its effects or regulation in tumor cells. The present studies were undertaken to investigate whether various extracellular calcium concentrations could modulate the expression of the tumor-associated antigen (TAA) recognized by monoclonal antibody (MAb) 44-3A6. It is highly expressed by the human lung adenocarcinoma cell line A549 and has been shown to be a 40-kD integral plasma membrane protein. Treatment of the A549 cell line with various concentrations of exogenous calcium showed a dose-dependent rise in the internal free calcium levels up to 2.4-2.9 mM (external calcium treatment). At higher concentrations, the internal calcium level showed a decline, indicating a higher calcium efflux. The calmodulin-dependent Ca(2+)-ATPase enzyme involved in calcium homeostasis was assayed under these same conditions. The enzyme activity increased with increasing external calcium concentrations showing a 5-fold increase in cells treated with 4.05 mM calcium. These data suggest that as the internal calcium approaches toxic levels, the Ca(2+)-regulated ATPase activity increases to reduce the calcium overload within the cell. Employing Western blot analysis and immunoperoxidase staining studies, this report shows that the antigen recognized by MAb 44-3A5 on A549 cells increased with an increase in calcium concentration. Evidence that this antigen is phosphorylated is presented using Western blot analysis of a radiolabeled antigen-enriched plasma membrane fraction. The previously reported subcellular localization, and now the phosphorylation and responsiveness to calcium by this TAA, gives it the properties predicted to be seen in a calcium 'pump-like' molecule. Thus, these studies support the hypothesis that this TAA may be important in intracellular calcium concentration control or that it is regulated via some calcium-mediated process.


Predicting return to work for lower back pain patients receiving worker's compensation.

The results of a prospective study of 134 patients with lower back pain suggest that nonorganic factors are better predictors of return to work than organic findings. Patients who returned to work had fewer job, personal, or family related problems. There were no significant differences between patients who returned to work and those who did not when comparing myelograms, computed tomographic scans, or roentgenographs. The only significant difference in physical organic findings was for muscle atrophy. Patients who did not return to work had a statistically higher incidence rate of muscle atrophy. Length of time off from work was significantly related to outcome, but when patients were categorized according to time off the job, different factors predicted failure to return for patients off work for less than 6 months and patients off for more than 6 months. For patients off for less than 6 months, important predictors were a high Oswestry score, history of leg pain, family relocation, short tenure on the job, verbal magnification of pain, reports of moderate to severe pain on superficial palpation, and positive reaction to a "sham" sciatic tension test. None of these was a significant predictor for the group off for more than 6 months. For the group off work for more than 6 months, previous injuries, and stability of family living arrangements were among the significant predictors not significant for the group off less than 6 months. Using 21 factors selected from a larger group of 92 factors, three statistically significant (P less than or equal to 0.001) predictive measures were developed. These measures predicted return to work for the total sample, and for the two subgroups (off more than, or less than 6 months) more accurately than did the total set of 92 factors.


Mobility, strength, and fitness after a graded activity program for patients with subacute low back pain. A randomized prospective clinical study with a behavioral therapy approach.

Patients with nonspecific mechanical low back pain (n = 103), examined by an orthopaedic surgeon and a social worker, were randomized to an activity group (n = 51) and a control group (n = 52). Patients with defined orthopaedic, medical, or psychiatric diagnoses were excluded before randomization. No patients were excluded due to place of birth or difficulties in speaking or understanding the Swedish language. The purpose of the study was to compare mobility, strength and fitness after traditional care and after traditional care plus a graded activity program with a behavioral therapy approach. A graded activity program, with a behavioral therapy approach was given under the guidance of a physical therapist. The endpoint of the graded activity program was return to work. This program significantly increased mobility, strength, and fitness more than could be explained by only a time recovery effect, especially in males. The patients in the activity group returned to work earlier than did the patients in the control group. Spinal rotation, abdominal muscle endurance time and lifting capacity were significantly correlated to rate of return to work. Traditional care plus a graded activity program were superior to only traditional care, evaluated in terms of mobility, strength and fitness. The graded activity program proved to be a successful method of restoring occupational function and facilitating return to work in subacute low back pain patients. The patients in the graded activity program learned that it is safe to move, while regaining function.


Serial lumbar dynamometry in low back pain.

To determine the significance of changes in motor performance as measured by lumbar dynamometry, serial lumbar dynamometry was performed on a group of 45 male Workers' Compensation patients with chronic "mechanical" low back pain and in a group of 20 healthy male volunteers. The patients were men aged 20-60 years, whose current episode of low back pain had lasted for at least 3 months (mean 19.5 weeks, range 12-47 weeks). Testing was performed at entry into a "back school" program of therapy and again 2 weeks and 4 weeks later. The control group showed a slight improvement in almost all variables of strength and range of motion between the first and second tests but no significant change between the second and third tests. This was consistent with a learning effect. The patient group was analyzed as a whole and also in two groups based on their response to the Waddell maneuvers at entry: Waddell score 0-2 (no excessive illness behavior) and 3-5 (excessive illness behavior). As a whole, the patients showed significant progressive improvement in most variables on successive tests. The group with the low Waddell score had significantly greater strength and range of motion than the group with the high Waddell score but the trend of improvement with time was similar in the two groups. The authors conclude that in this sample of patients with low back pain, serial lumbar dynamometry reveals a progressive improvement in performance, which is greater than the improvement expected from the natural history of physical recovery and greater than the improvement expected from an increase in strength and range of motion attributable to the therapeutic exercises performed and is much larger than any learning effect related to the test procedure.


Low back and neck/shoulder pain in construction workers: occupational workload and psychosocial risk factors. Part 1: Relationship to low back pain.

The prevalence rate of musculoskeletal problems, especially low back pain and severe low back pain in a randomly selected sample of 1,773 construction workers was studied. Its relationship to physical and psychosocial factors was analyzed. The workers answered a postal questionnaire. Workload was measured by means of eight manual materials handling indices and ten psychosocial indices, based on results from factor analyses. The 1-year prevalence rate of low back pain was 54% and of severe low back pain 7%. The relationship to heavy manual materials handling differed with age in such a manner that it could be interpreted as a healthy worker effect. Between severe low back pain and both stooping or kneeling a dose-response relationship was found. The most prominent of the psychosocial factors associated with low back pain and severe low back pain were the stress index and the psychosomatic and psychic indices. The age-standardized prevalence rate ratio of low back pain was 1.6 (95% confidence interval 1.4-1.8) and for severe low back pain 3.1 (95% confidence interval 2.3-4), when workers reporting "high" stress were compared to workers reporting "low" stress.


Low back and neck/shoulder pain in construction workers: occupational workload and psychosocial risk factors. Part 2: Relationship to neck and shoulder pain.

The prevalence rate of neck and shoulder trouble and considerable neck and shoulder pain in a randomly selected sample of 1773 construction workers were studied. The relationship to physical and psychosocial factors was analyzed. The workers answered a postal questionnaire. Workload was measured by means of eight manual materials handling indices and ten psychosocial indices, based on results from factor analyses. The 1-year prevalence rate of considerable neck and shoulder trouble was 56% and of neck and shoulder pain 12%. To work with hands above shoulder level showed a dose-response relationship to both neck and shoulder trouble and neck and shoulder pain. The psychosocial factors were more prominently associated with neck and shoulder trouble and neck and shoulder pain than the physical workload factors. The psychosocial indices; psychosomatic and psychic symptoms, stress and job satisfaction showed the highest age-standardized prevalence rate ratios for both neck and shoulder trouble and neck and shoulder pain.


Chronic cocaine enhances serotonin autoregulation and serotonin uptake binding.

Repeated cocaine intoxication can result in the development of behavioral sensitization in animals and psychosis in humans, phenomena that have been associated with alterations in dopamine (DA) function. Using electrophysiologic and autoradiographic techniques, modifications of central serotonin (5-hydroxytryptamine; 5-HT) systems were investigated in rats treated with a regimen of cocaine administration that produced behavioral sensitization. The inhibitory response of single 5-HT neurons in the dorsal raphe (DR) to (-)-cocaine, the 5-HT uptake inhibitor fluoxetine or the 5-HT1A agonist 8-hydroxy-2-[di-N-propylamino]tetralin (8-OHDPAT) was significantly enhanced in cocaine-treated rats. Furthermore, several brain areas that contain either cell bodies (DR) or terminals for 5-HT (medial and sulcal prefrontal cortex, frontal cortex) showed cocaine-induced elevations in [3H]imipramine-labeled 5-HT uptake sites, while [3H]-8-OHDPAT-labeled 5-HT1A receptors were decreased only in the central medial amygdala. These results suggest that modifications of autoregulatory mechanisms secondary to alterations of 5-HT uptake processes may contribute to the development of cocaine sensitization.


[123/125I]RTI-55, an in vivo label for the serotonin transporter.

[123I]RTI-55, an iodinated derivative of the cocaine analog 3 beta-phenyltropane-2 beta-carboxylic acid methyl ester, was evaluated as an agent for in vivo labeling of the serotonin transporter. Labeling of the precursor of RTI-55 with I-123 was efficient and yielded a high specific activity product. After intravenous injection of [123I]RTI-55 into rats, the tracer accumulated in regions with high densities of serotonin and dopamine uptake sites. The distribution of [123I]RTI-55 binding in areas rich in serotonin uptake sites correlated with [3H]serotonin uptake measured in vitro in the same regions. Specific [123I]RTI-55 binding to serotonin uptake sites was inhibited by paroxetine but not by GBR 12,909. Treatment of rats with neurotoxic doses of fenfluramine caused decreases of 66% (in the hypothalamus) to 83% (in the superior colliculi) of specific [125I]RTI-55 binding in all areas except in the striatum and the olfactory tubercles (regions rich in dopamine transporters). These results indicate that [123/125I]RTI-55 binds, although not selectively, to the serotonin transporter in vivo. Furthermore, they suggest that [123I]RTI-55 holds promise as a SPECT imaging agent for the study of the serotonin transporter in humans in health and disease.


Topographic nonoverlapping distribution of D1 and D2 dopamine receptors in the amygdaloid nuclear complex of the rat brain.

The distribution of D1 and D2 dopamine (DA) receptors in the nuclei and subnuclear zones of the rat amygdaloid complex was mapped using quantitative light microscopic autoradiography. [125I]iodosulpiride and [125I]SCH 23982 (in the presence of 50 nM ketanserin) were used to label D2 and D1 DA receptors, respectively. The DA receptor subtypes exhibited a topographic, nonoverlapping distribution which generally conformed to the cytoarchitectonic boundaries of the component nuclei and subnuclear zones of the amygdaloid complex. The highest density of [125I]iodosulpiride binding sites was observed in the main intercalated cell group and the central amygdaloid nucleus where a medial to lateral gradient of binding sites was localized to its subnuclear zones. [125I]SCH 23982 binding sites were localized in the main intercalated cell group and the basolateral amygdaloid nucleus with a uniform low density in the central nucleus. The functional topography of mesoamygdaloid DA neurons may therefore be mediated, in part, at the level of DA receptor subtypes. The pattern of distribution of [125I]iodosulpiride binding sites in subdivisions of the central amygdaloid nucleus and bed nucleus of the stria terminalis suggests that the functions of the "extended amygdala," a major system of the functional organization of the basal forebrain, may be regulated by DA afferents at multiple key sites of D2 receptor action.


Identification of murine thymocyte populations capable of extensive proliferation in serially passaged thymic organ cultures.

Using the approach of titrating precursor cells into mouse thymus organ cultures and serial passage, we have sought to compare the proliferative capacities of cells derived from adult and embryonic thymus and related haemopoietic tissues. We find that cells derived from the liver and thymus of day 14 embryos are capable of extensive proliferation in such cultures (surviving for at least 12 weeks) whereas cells derived from adult sources (blood and thymus) display a much more restricted lifespan and potential for division. Analysis of sequentially passaged thymic lobes shows that cells lacking CD4 and CD8 (CD4- and CD8-) and a subset of single CD8 positives are selectively expanded in these cultures. A preliminary study of the CD4-CD8- populations in these lobes suggest that these include cells expressing surface CD3 (in association with either TCR alpha beta or TCR gamma delta) and a subset of CD4-CD8-CD3-. These findings suggest that sequential passage of thymocytes in organ culture may be a useful alternative strategy for characterising cells with high proliferative potential, resident in the thymus and also for probing their lineage relationships.


Observations on lymphomagenesis and lymphoma in AKR mice. A description of prelymphoma changes in the thymus and phenotypic diversity of lymphomas induced by SL3-3 virus.

These studies were designed to look for a correlation of intrathymic survival of virus-infected thymocytes with lymphomagenesis. Cells from the normal-appearing prelymphoma thymus of SL3-3 virus-treated AKR mice were studied. Also, phenotypic properties of the malignant cells from the virus-induced lymphomas are described. In this model system, 100% of mice inoculated with virus at three days of age develop thymic lymphoma between 60 and 90 days of age. The experiments show that cells with malignant potential do not appear in the thymus until 36 days after virus inoculation. These cells are initially thymus-dependent (TD) in that they produce lymphoma of donor-type in recipients after intrathymic inoculation with long latency. They do not produce lymphoma after subcutaneous inoculation in syngeneic hosts. At 39 days after virus inoculation, the first thymus independent (TI) lymphoma cells appear. These cells, like the cells isolated from thymi with overt tumors, produce lymphoma of donor-type after a short latency when inoculated by the intrathymic or subcutaneous route. Thymocytes from normal-appearing thymi of mice at 42 days after virus inoculation, which could be expected to include TD, TI or no lymphoma cells, were evaluated for their ability to survive in a recipient thymus for three weeks after intrathymic inoculation. They were compared to thymocytes from age-matched control mice. Thymi receiving the virus-infected thymocytes showed 15% to 80% donor cells at three weeks. The highest numbers of donor cells were from thymi which were shown to contain TI lymphoma cells. However, cells from thymi with TD and no lymphoma cells could also be detected in significant numbers at three weeks after intrathymic inoculation. Less than 2% of donor-type thymocytes could be found after inoculation of thymocytes from normal control AKR mice. These data provide evidence that virus infection of thymocytes, even before the appearance of cells with lymphomagenic potential, endows them with a capacity for prolonged intrathymic survival. This appears to be a necessary step for tumor progression in this model. A remarkable phenotypic diversity of the virus-induced lymphomas was shown. The effect of various growth environments, intrathymic, subcutaneous, and in vitro on lymphoma cell phenotypic expression revealed individual differences in each tumor and in each environment.


Experimental atrophic rhinitis in 2 and 4 month old pigs infected sequentially with Bordetella bronchiseptica and toxigenic type D Pasteurella multocida.

Experimental infections with Bordetella bronchiseptica and/or toxigenic type D Pasteurella multocida were studied in 2- and 4-month-old primary specific-pathogen-free pigs. None of the 2-month-old pigs inoculated with B. bronchiseptica or P. multocida alone developed turbinate atrophy. All the pigs inoculated with B. bronchiseptica (10(7) CFU/head) and P. multocida (10(9) CFU/head for 5 consecutive days) together, however, developed clinical and post-mortem signs of atrophic rhinitis (AR) similar to the naturally occurring disease. Slight to severe turbinate atrophy was observed in the 4-month-old pigs inoculated with B. bronchiseptica and P. multocida (at the same concentration as above) at necropsy.


[Characteristics and results of the determination of the doses of internal irradiation of the thyroid gland in the population of contaminated districts of the Byelorussian Republic].

The authors provide the results of studying the reconstruction of individual doses of thyroid radiation among the community living in polluted areas of the Byelorussian Republic according to radiation monitoring data and with regard to the nature of radioactive pollution of the land. Every individual result of estimating the degree of thyroid radiation was characterized by 3 magnitudes: the lower and upper limit of possible values and by the intermediate (basic) value. The authors hold that studies of the correlations between the values of individual doses of thyroid radiation and different parameters of the radiation situation in every region will promote further specification of individual doses of thyroid radiation.


[The mechanism of milk contamination in the territory of Gomel Oblast].

The authors provide the results of studying 137Cs and 90Sr pollution of soil, plants and milk in the Gomel region in 1986-1989. Describe the dynamics of the ratios soil-grass and milk-soil during that period. The content of 137Cs in milk ranged from n.10(-10) to n.10(-7) Ci/l in polluted regions and from n.10(-10)-n.10(-9) Ci/l in the so-called pure regions. In all the regions examined, the concentration of 90Sr in milk was far lower than that of 137Cs. After the accident the levels of 137Cs in milk rose 18-350-fold and those of 90Sr 3-16-fold on the average in the regions. One can observe a progressive decrease of the ratios of accumulation in the grass-soil and milk-soil systems and a decline of the concentration of 137Cs and 90Sr in milk. However, the percentage of samples with an increase of the temporarily permissible in 1988 levels of cesium radionuclides was fairly high in 1989 in certain regions: in the Vetkovsk region, it was 35.3%, in the Chechersky region, it was 28.0%. During 1987-1989, the concentration of 90Sr in milk did not exceed 1 x 10(-9) Ci/l in the areas examined. The broad range of the indicators of milk pollution with 137Cs and 90Sr is specified by varying density of the area pollution, differences in the physicochemical status of radionuclides in accident fall-outs, and geochemical characteristics of the soil sheet.


Left ventricular hypertrophy: an initial response to myocardial injury.

The prevailing wisdom generally has been that the failing heart hypertrophies in response to increased wall stress. The increase in myocardial mass observed in heart failure is therefore a relatively late compensatory event geared to normalize wall stress. Although this is undoubtedly true, especially for heart failure resulting from a large anterior myocardial infarction accompanied by rapid left ventricular expansion, it is possible that an important form of hypertrophy occurs much earlier as an initial response to myocardial injury. One can hypothesize that the initial response to injury is a nonspecific phenotypic alteration of the cardiac myocyte to one of growth and development. Such changes may be driven by both trophic and mechanical forces and may be important in altering the architecture of the myocardial cell and surrounding cardiac interstitium. Preliminary data from a variety of models support the concept that neuroendocrine activity is an important component in the ventricular remodeling process, and that pharmacologic interventions designed to block systemic and tissue neuroendocrine activity may prevent excessive cardiac enlargement and its ultimate consequences. Because this concept has important implications for preventive cardiology, the results of several prevention trials, including the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS), Studies of Left Ventricular Dysfunction (SOLVD), and Survival and Ventricular Enlargement (SAVE) are awaited eagerly.


Insulin-dependent diabetes mellitus in native Estonians and immigrants to Estonia.

The authors compared the epidemiology of childhood insulin-dependent diabetes mellitus in Estonia during 1980-1989 between native Estonians and an immigrant group that consisted mainly of Russians. The average annual incidence of diabetes mellitus was significantly higher in Estonians (11.8 per 100,000 children aged less than 15 years; 95% confidence interval (CI) 10.4-13.3) than in non-Estonians (7.6 per 100,000 children aged less than 15; 95% CI 6.2-9.4). This difference appeared in both sexes. The highest incidence in both Estonians and non-Estonians was recorded in 1982, when the incidence in the immigrant population was twice as high as the baseline level. These data indicate that immigrant populations need not acquire the same risk of insulin-dependent diabetes as the native population.


The thrombotic diathesis associated with the presence of phospholipid antibodies may be due to low levels of free protein S.

To determine if abnormalities in the protein C/protein S anticoagulant system exist in patients with phospholipid antibodies who had the primary clinical complaint of fetal wastage. Eleven patients with fetal wastage and phospholipid antibodies were selected for study. Some patients also gave a history of previous thrombotic events related to oral contraceptives and/or pregnancy, but patients were not selected because of a history of clinical thrombosis. The levels of protein C (chromogenic assay), protein S (both free and bound) (Laurell rocket), and C4b-binding protein (Laurell rocket) were measured, and assays for the presence of antibodies against protein S or protein C were performed. Seven of the 11 patients were found to have low levels of free protein S. Total protein S and protein C levels were within the normal range in all patients. Antibodies to protein C and protein S were not found in any patient. These findings suggest that free protein S levels may be abnormally low in some patients with phospholipid antibodies. Free protein S levels are abnormally low in some patients with phospholipid antibodies, and this abnormality may be a factor contributing to the thrombotic diathesis associated with phospholipid antibodies.


Differences in vitamin D status between countries in young adults and the elderly.

To compare vitamin D status between countries in young adults and in the elderly. Reports on vitamin D status (as assessed by serum 25-hydroxyvitamin D) from 1971 to 1990 were reviewed. Studies were grouped according to geographic regions: North America (including Canada and the United States); Scandinavia (including Denmark, Finland, Norway, and Sweden); and Central and Western Europe (including Belgium, France, Germany, Ireland, The Netherlands, Switzerland, and the United Kingdom). Vitamin D status varies with the season in young adults and in the elderly, and is lower during the winter in Europe than in both North America and Scandinavia. Oral vitamin D intake is lower in Europe than in both North America and Scandinavia. Hypovitaminosis D and related abnormalities in bone chemistry are most common in elderly residents in Europe but are reported in all elderly populations. The vitamin D status in young adults and the elderly varies widely with the country of residence. Adequate exposure to summer sunlight is the essential means to ample supply, but oral intake augmented by both fortification and supplementation is necessary to maintain baseline stores. All countries should adopt a fortification policy. It seems likely that the elderly would benefit additionally from a daily supplement of 10 micrograms of vitamin D.


Education and engineering solutions for potential problems with laparoscopic monopolar electrosurgery.

The potential problems of monopolar electrosurgery relate to unrecognized energy transfer ("stray current") outside the view of the laparoscope. Mechanisms of stray current and unrecognized tissue injury include: (1) insulation breaks in electrodes; (2) capacitive coupling, or induced currents through the intact insulation of the active electrode to surrounding cannulas or other instruments; and (3) direct coupling (or unintended contact) between the active electrode and other metal instruments or cannulas within the abdomen. Capacitive coupling poses the greatest risk for injury when the outer conductor (trocar cannula or irrigation cannula) is electrically isolated from the abdominal wall by a plastic nonconductor. Capacitive coupling is increased by the coagulation mode (versus cut), open circuit (versus tissue contact with the electrode), 5-mm cannulas (versus 11 mm), and higher voltage generators. The safety of electrosurgery can be enhanced by surgical education regarding the biophysics of radio frequency electrical energy, technical choices in instruments using all-metal cannula systems, and engineering developments with a dynamically monitored system for insulation failure and capacitive coupling.


A new technique for indirect inguinal hernia repair.

This report concerns a preliminary study of a new technique for indirect herniorraphy, which was used in 242 patients from December 1988 through March 1991. Its main characteristics are the creation of a deep neo-inguinal ring in a more medial site, shortening of the inguinal canal by transposition of the superficial ring to the point where the inferior border of the internal oblique muscle is well represented, reinforcement of the inguinal canal by overlapping the external oblique aponeurosis in a double-breast fashion, and maintenance of the cremasteric muscle. Follow-up in our outpatient clinic was carried out at 1, 6, 12, and 24 months in 71% of our patients. There were no recurrences, except for one crural pseudo-recurrence, no mortality, and no testicular atrophy. Thirteen percent of patients had subcutaneous serous collection; 1% had hematomas; 2% temporary testicular edema; and 0.4% wound infection.


Positron emission tomography in the Rett syndrome: clinical, biochemical and pathological correlates.

A consistent constellation of clinical signs and symptoms define the Rett syndrome, the most prominent of which are disorders of movement and tone. Preliminary pathologic and neurochemical data indicate predominant involvement of the nigrostriatal dopaminergic pathways and the cholinergic system of the basal forebrain region. The age of onset differentiates the Rett syndrome from Alzheimer and Parkinson disease with similar lesions. PET scanning makes it possible to relate the chemistry of the brain to function by measuring the number and affinity of neuroreceptors, metabolism in specific brain regions, and provide important determinants of the underlying mechanisms in disease states.


Isradipine and other calcium channel antagonists attenuate ethanol consumption in ethanol-preferring rats.

The present work is concerned with studying of the ability of different calcium channel antagonists to modify voluntary ethanol ingestion by rats selectively bred for high ethanol preference. The compounds were given s.c. thrice daily for 5 days at doses that did not produce locomotor impairment. While nifedipine, darodipine, and verapamil (each at the dose of 20 mg/kg thrice daily) produced a modest reduction in ethanol intake, isradipine (at the dose of 1 mg/kg three times a day) reduced ethanol intake by over 70%. For all compounds, the reduction in ethanol intake was compensated by a proportional increase in water consumption and the inhibitory effect persisted throughout the 5 days of treatment. The data indicate that calcium channel antagonists exhibit quite different potency in reducing ethanol preference, however this action is a general property of this class of compounds.


The involvement of NMDA receptors in acute and chronic effects of ethanol.

Recent evidence indicates involvement of excitatory amino acid receptors sensitive to N-methyl-d-aspartate (NMDA) in the action of ethanol (EtOH). Pronounced inhibition of NMDA receptor function is seen in vitro with concentrations of EtOH corresponding to those present during alcohol intoxication in humans. The present study was devoted to investigate the role of NMDA receptors in the action of EtOH in rats. Acute experiments showed antagonism by EtOH of convulsions induced by intracerebroventricular injection of NMDA. A similar effect was seen with a high dose of diazepam. Convulsions induced by an agonist of another excitatory amino acid receptor subtype, kainate, were also inhibited by EtOH. An uncompetitive antagonist of NMDA receptors, 5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine maleate (MK-801), potentiated EtOH-induced loss of righting, but attenuated the hypothermic action of EtOH. Moreover, MK-801 inhibited audiogenic convulsions in EtOH withdrawn rats. At the same time the effect of a proconvulsive dose of NMDA was not enhanced. Tolerance to the myorelaxant action of both EtOH and MK-801 upon repetitive administration was seen. Also some degree of cross-tolerance was observed. Moreover, MK-801 failed to modify EtOH preference in rats. The present results support involvement of NMDA receptors in expression of some acute and subchronic actions of EtOH and in expression of EtOH withdrawal.


Clinical evaluation of doxacurium chloride.

Doxacurium was administered to 50 adult patients for determination of potency (n = 10), onset and duration of clinical relaxation (n = 40). Cumulative dose-response showed the ED95 to be 33.24 micrograms.kg-1 (95% confidence limits 27.4-39.3). Doxacurium 33 micrograms.kg-1 was then administered to four groups of 10 patients each who had anaesthesia maintained with either fentanyl-droperidol or halothane and nerve stimulation carried out with single-twitch stimulation at 0.1 Hz or train-of-four stimulation at 2 Hz every 12 s. The onset and duration showed wide individual variation. The mean (SD) times to occurrence of maximal block were 8.5 (4.6), 6.1 (1.9), 6.7 (1.8) and 4.7 (1.3) min in the single twitch-fentanyl, train-of-four--fentanyl, single twitch-halothane and train-of-four--halothane groups respectively, although it ranged from 3.4 to 13.1 min in individual patients. The mean (SD) durations of clinical relaxation (recovery of single twitch or first response in train-of-four to 25%) were 65 (22.8), 52 (21.7), 70 (33.4) and 72 (21.0) min respectively with individual values ranging from 31 to 103 min. Although halothane administration increased the duration of clinical relaxation and train-of-four stimulation accelerated the onset of effect, the changes due to these were not significant. There were no adverse effects on heart rate or indirectly measured arterial pressure.


Carbon dioxide pneumothorax occurring during laparoscopic cholecystectomy.

A previously fit patient underwent laparoscopic cholecystectomy. During the procedure arterial oxygen saturation fell and clinical examination revealed signs of a right pneumothorax confirmed by chest X ray. Aspiration of the pleural cavity and analysis of the gas removed showed it to be composed entirely of carbon dioxide. Possible mechanisms of entry of carbon dioxide into the pleural space are discussed.


Double-blind study of intranasal ipratropium bromide in nonallergic perennial rhinitis.

We undertook this trial to determine whether ipratropium bromide nasal spray 0.03% (IB) reduced the nasal hypersecretion associated with nonallergic perennial rhinitis (NAPR) without causing excessive dryness or irritation of the nasal mucosa. We compared two drug doses of IB (21 micrograms and 42 micrograms per nostril) to a placebo, administered as two sprays to each nostril twice daily. The study design consisted of a 1-week screening period without treatment, a 1-week single-blind placebo period, a 4-week double-blind treatment comparison period, and a 1-week follow-up period without medication to evaluate nasal rebound. One hundred fifty-two patients were entered and 140 completed the trial. Both doses of IB reduced the severity and duration of rhinorrhea compared with placebo (P = .05 and .03, respectively). Treatment differences were noticeable during the first week of therapy, continued to widen during the second week, and then remained stable throughout the next 2 weeks. There was no evidence of nasal rebound observed during the week after treatment. The drug was well tolerated with side effects limited to infrequent nasal adverse events of nasal dryness, blood-tinged mucus, and epistaxis occurring in 2% to 6% of patients. We conclude that IB is a safe and effective therapy for control of rhinorrhea associated with NAPR.


Inoculation of conventionally and specific-pathogen-free reared rabbits with Ostertagia ostertagi isolated from cattle.

Eleven trials were conducted to collect helminthologic and pathologic data from 27 conventionally reared (CR) and 53 specific-pathogen-free (SPF) 6- to 13-week-old male New Zealand White rabbits. These rabbits were given 50,000 to 100,000 ensheathed third-stage infective Ostertagia ostertagi larvae (L3) orally. The L3 had been isolated from the feces of cattle. Fecal egg counts were conducted and worm populations were determined after euthanasia 3 to 56 days after inoculation. At necropsy, nodules were observed in a confluent pattern in the mucosa of cardiac region of the stomach in all inoculated rabbits, except in CR rabbits inoculated at 6 weeks of age, which had no nodules or worm burdens 42 days after inoculation. Confluent areas were not observed in SPF rabbits euthanatized 5 days or less after inoculation; however, small, transparent nodules were evident in the mucosa of the cardiac region of the stomach. Fourth-stage larvae (L4) were obtained from the mucosal nodules after digestion of stomach of both types of rabbits. There were more L4 in SPF than CR rabbits. In addition, greater numbers of L4 were found in SPF rabbits euthanatized 14 days or less after inoculation. Petechial hemorrhages were in the fundic area of the stomach mucosa in SPF rabbits inoculated with 100,000 L3 and euthanatized 14 days later. Mature O ostertagi or worm eggs in feces were not found in inoculated CR or SPF rabbits. The pathologic changes had characteristics similar to those in cattle and goats infected with O ostertagi.(ABSTRACT TRUNCATED AT 250 WORDS)


Abdominal muscle use during breathing in patients with chronic airflow obstruction.

To assess the pattern of abdominal muscle contraction in stable patients with chronic obstructive pulmonary disease (COPD), we studied electromyograms of the rectus abdominis, external oblique, and transversus abdominis muscles in 40 patients with variable degrees of chronic airflow obstruction (FEV1 between 17 and 82% of predicted); 12 control subjects with normal pulmonary function tests were studied for comparison. The subjects were studied during resting breathing in the supine posture, and the electromyograms were recorded with concentric needle electrodes implanted with the aid of a high-resolution ultrasound. The rectus abdominis and external oblique were silent in virtually all patients. In contrast, 17 patients had invariable phasic expiratory activity in the transversus abdominis, and 11 additional patients had intermittent transversus expiratory activity. Expiratory contraction of the transversus was related to the degree of airflow obstruction (p less than 0.005), and when present, it persisted in the seated posture. We conclude that (1) when breathing at rest, many stable patients with severe chronic airflow obstruction contract the abdominal muscles during expiration, and (2) this expiratory contraction is usually confined to the transversus muscle. These observations also indicate that the physiology of dynamic hyperinflation and intrinsic positive end-expiratory pressure (PEEP) in such patients should be reevaluated.


Potential role of immunomodulators for treatment of phlebovirus infections of animals.

Rift Valley fever (RVFV) is a major phlebovirus-induced epizootic disease of domestic animals (primarily cattle and sheep) in Africa. No therapies for the disease are known. A related phlebovirus, Punta Toro virus (PTV), has been adapted to induce an RVFV-like disease in C57BL/6 mice. This PTV infection has been used as a model for RVFV because it is reasonably safe and does not require high-level biologic containment. The infection model has been used to study the potential role of immunomodulating substances as therapies. A spectrum of immunomodulators has been studied; those immunomodulators most capable of preventing death and other disease manifestations are ampligen, bropirimine, poly (ICLC), AM-3, P-136, and 7-thia-8-oxoguanosine. An immunologic parameter common to all these substances has been their ability to induce interferon. Timing studies have indicated that these active substances may be administered therapeutically as well as prophylactically to inhibit markedly the progress of the disease. Further work is needed in the development of these materials for use in treating viral infections in domestic animals. As a next step, studies need to be run to compare the immunologic profiles induced by each substance in domestic animals and in mice.


[Co-operative clinical evaluation of 5'-DFUR tablets for breast cancer at 31 institutions].

A phase II study of 5'-deoxy-5-fluorouridine (5'-DFUR) tablets for breast cancer was done at 31 institutions in Japan. Forty-five patients were registered and 44 of them were eligible for the study. Of the 40 patients whose results could be evaluated, 11 (28%) responded (four complete responses and seven partial responses). Side effects, such as diarrhea, anorexia, leukocytopenia, and liver dysfunction were observed in 24 of the 44 patients. The side effects were mild and transient. 5'-DFUR is a promising drug for breast cancer treatment, and its tablet form makes chemotherapy easier for the patient.


[A case of advanced breast cancer responding to low-dose 5'-DFUR].

A 69-year-old female patient with locally advanced breast cancer with multiple bone metastases (T4cN2-M1) was treated with 5'-DFUR after failure of tamoxifen treatment. The 5'-DFUR dose was limited to 600 mg per day, half the usual dose, because of its gastroenterological side effects. The primary tumor and metastatic axillary lymph nodes regressed three months after the start of treatment, and the complete remission of lesions was obtained in 16 months. Reduction of bone metastasis was confirmed by the disappearance of osteolytic lesion in the skull roentgenogram and the decrease of abnormal accumulation on the bone scintigram. Serum levels of CEA and ST-439 markedly reduced during the treatment as the disease regressed.


[A case report; 5'-DFUR reduced gastric cancer with multiple liver metastasis].

We describe a case of gastric cancer with multiple liver metastasis that clearly decreased in size after administration of 5'-DFUR. The patient (a 63-year-old male) was inoperable because of multiple liver metastasis. 5'-DFUR 600 mg/day reduced the size of the multiple liver tumors (reduction rate 90%, partial response for four months), but the gastric tumor was unaltered. A rapid decrease in alkali-phosphatase indicated reduction of the liver tumors only one week after the initiation of 5'-DFUR.


The Scottish low birthweight study: I. Survival, growth, neuromotor and sensory impairment.

Of all 908 livebirths weighing less than 1750 g at birth who were born in Scotland in 1984, 896 (99%) were enrolled in a prospective study to document survival and determine the prevalence of neuromotor and sensory impairments and disability. At the age of 4.5 years, 636 (71%) had survived and 611 (96%) were assessed. Overall 16% were disabled; 47 had cerebral palsy (52.5/1000 livebirths), seven were blind (7.8/1000 livebirths), and 11 were deaf and using aids (12.3/1000 livebirths). Among those not overtly disabled, the prevalence of poor neuromotor competence was high and related to birth weight. All growth measures had mean values below the standard population mean indicating a downward shift in the distribution which was related to birth weight. In addition the height distribution was negatively skewed.


Drug treatment of canine acral lick. An animal model of obsessive-compulsive disorder.

Canine acral lick dermatitis is a naturally occurring disorder in which excessive licking of paws or flank can produce ulcers and infection that require medical treatment. Forty-two dogs with severe chronic canine acral lick dermatitis were treated in three double-blind crossover comparisons of clomipramine hydrochloride/desipramine hydrochloride, fluoxetine hydrochloride/fenfluramine hydrochloride, and sertraline hydrochloride/placebo. The serotonin uptake blocking drugs were clinically effective, while the other drugs were not. Based on phenomenology and pharmacological response, we propose canine acral lick dermatitis as an animal model of obsessive-compulsive disorder.


Microleakage of glass ionomer/composite resin restorations: a laboratory study. Part 2. The influence of bonding systems.

Acid-etching and bonding of composite resin to bevelled enamel margins has been reported to produce a reliable seal. However, achieving a seal with dentine and cementum margins is more difficult. Four different dentine bonding systems were used in combination with Silux composite resin to restore cervical cavities in vitro. None of the bonding systems used completely sealed either the occlusal or gingival margins. Of the four systems, GLUMA provided the best seal at both the occlusal and gingival margins.


A laboratory investigation of a composite resin/dentine bonding agent mixture used as a root canal sealer.

The objective of this project was to determine the effectiveness of a dentine bonding agent, in conjunction with a composite resin, to act as an endodontic sealing material. The effectiveness was compared with that provided by a conventional sealer (AH26) by measuring dye penetration into the root canal. Two obturation techniques were used with each sealer; the single gutta-percha point technique, and lateral condensation with multiple gutta-percha points. Lateral condensation with the conventional sealer was found to be the superior procedure, by producing the least amount of linear leakage (coronally from the apex) on average. However, the single point technique with the composite resin/dentine bonding agent sealer provided the greatest number of 'no leakage' samples. Scanning electron microscope investigation of obturated roots revealed the presence of resin tags in dentine tubules only in those samples where the composite resin/dentine bonding agent sealer was used. The short working time provided by the composite resin/dentine bonding agent sealer prevented successful obturation using lateral condensation. The provision of an extended working time composition for this sealer may produce more favourable results in obturation with lateral condensation.


Severe problem behaviors related to social interaction. 1: Attention seeking and social avoidance.

Studies concerning the functional analysis of severe problem behaviors have suggested that it is important to identify the different categories of stimuli that control problem behavior because each has unique treatment implications. The present study explored the differential effects of adult attention on the severe problem behaviors of two groups of children with developmental disabilities. A third group of nonproblem children was examined for comparison purposes. Children participated in three experimental conditions in which the level of adult attention was manipulated: noncontingent high attention, noncontingent low attention, and contingent attention. Results validated the existence of two groups of children who differed as to their social orientation: (a) One group of children commonly initiated social interactions and was most likely to exhibit problem behaviors under conditions of low adult attention, and (b) the other group of children rarely initiated social interactions and exhibited frequent problem behaviors under conditions of high adult attention. Implications of these data for escape and attention theories of child problem behavior are discussed, as are the applied implications for reinforcer assessment and teaching strategies.


Severe problem behaviors related to social interaction. 2: A systems analysis.

The effects of problem behavior displayed by two groups of children with developmental disabilities was investigated. One group of children exhibited problem behavior under conditions of low adult attention and was referred to as the attention-seeking or AS behavior profile group. A second group of children exhibited problem behavior under conditions of high adult attention and was referred to as the socially avoidant or SA behavior profile group. A third group of nonproblem children (NP) was examined for comparison purposes. Pairs of children were placed in a teaching situation, and the effects of child problem behavior upon adult instructional behavior were measured. Results indicated that child behavior affected adult behavior and that different child behavior profiles affected adults differentially. Adults responded to the problem behaviors of the AS behavior profile group by increasing attention, providing higher levels of physical contact, and presenting academic tasks that required continuous adult-child interaction. Conversely, the same adults responded to the problem behaviors of the SA behavior profile group by reducing attention, providing lower levels of physical contact, and presenting academic tasks that required little adult-child interaction. The data indicated that these child effects were powerful, immediate, and durable. Theoretical implications concerning reciprocal social influence and the operant theory of child problem behavior are discussed. Applied implications concerning treatment selection and maintenance are also explored.


Hepatocyte growth factor rapidly induces the tyrosine phosphorylation of 41-kDa and 43-kDa proteins in mouse keratinocytes.

We have examined the hepatocyte growth factor (HGF)-mediated changes in protein-tyrosine phosphorylation in mouse keratinocytes (PAM-212) and canine kidney epithelial cells (MDCK). In PAM-212 cells HGF and epidermal growth factor, both of which stimulated the DNA synthesis, rapidly induced the tyrosine phosphorylation of two 41-kDa and two 43-kDa proteins: increased tyrosine phosphorylation of those proteins has been commonly observed when quiescent fibroblasts are stimulated with a variety of mitogenic agents. In contrast, HGF did not stimulate the DNA synthesis but induced cell dissociation in MDCK cells; under this condition, increased tyrosine phosphorylation of the 41-kDa and 43-kDa protein was not observed. A possible role of the increased tyrosine phosphorylation of 41-kDa and 43-kDa protein in the signaling pathway of HGF is discussed.


Evaluation of a Mycoplasma gallisepticum strain exhibiting reduced virulence for prevention and control of poultry mycoplasmosis.

Two experiments were conducted to evaluate the virulence and vaccination efficacy of a Mycoplasma gallisepticum (MG) isolate designated MG Intervet 6/85. Virulence of the strain was determined by evaluation of airsacculitis scores following aerosol exposure to the isolate before and after 10 sequential passes in either commercial broiler chickens or commercial turkeys. Two-week-old specific-pathogen-free chickens were vaccinated by aerosol exposure. The birds were challenged with the R' strain of MG at either 4 or 8 weeks post-vaccination. Efficacy was evaluated by airsacculitis scores determined 21 days after challenge. Ten repetitive back-passes of the isolate in chickens and turkeys did not substantially increase the virulence. Virulence for both chickens and turkeys was minimal, while protection elicited by aerosol vaccination in young chickens against virulent R' strain was significant (P less than or equal to 0.05) compared with unvaccinated controls.


Metabolic fate of nicotinamide in LEC rats.

Metabolic fates of nicotinamide in Wistar and LEC rats were compared. In Wistar rats (normal rats) nicotinamide was generally catabolized to N1-methyl-4-pyridone-3-carboxamide (4-Py) through N1-methylnicotinamide (MNA). But in LEC rats nicotinamide catabolism mainly stopped at MNA. Therefore, the excretion ratio of (N1-methyl-2-pyridone-5-carboxamide + 4-Py)/MNA, which is an index of amino acid adequacy, was much lower in the LEC rats than in the Wistar rats. This phenomenon was attributed to the fact that the 4-Py-forming MNA oxidase activity was much lower in the LEC rats than in the Wistar rats. The NAD contents in liver and blood were also lower in LEC rats than in Wistar rats. These results suggest that the ability to synthesize proteins such as 4-Py-forming MNA oxidase and dehydrogenases may be impaired in LEC rats.


Serological response of chickens to infection with Salmonella gallinarum-S. pullorum detected by enzyme-linked immunosorbent assay.

The serological response to Salmonella pullorum and S. gallinarum infection in chickens was studied with an indirect enzyme-linked immunosorbent assay (ELISA). In broiler chickens, a more virulent strain of S. pullorum produced a significantly lower serum IgG titer than did a less virulent strain. In laying hens, the serum and egg-yolk IgG titers were very similar. In chickens infected with S. gallinarum, high IgG titers persisted for 30 weeks. In chickens reinfected with this strain, each reinfection was followed by transitory increases in IgG lasting no longer than 2 weeks. Serum samples from Brazil taken from a laying flock with evidence of fowl typhoid showed much higher antibody levels than did those from three uninfected flocks. Using lipopolysaccharide as the detecting antigen, infections caused by these salmonellae could be differentiated from those caused by other groups. Incorporation of the appropriate flagella antigen in the ELISA allowed differentiation between infections caused by S. pullorum and S. enteritidis.


Inhibition of gastric mucosal laminin receptor by Helicobacter pylori lipopolysaccharide: effect of ebrotidine.

The effect of lipopolysaccharide from H. pylori, a bacteria implicated in the etiology of gastric disease, on the gastric mucosal laminin-receptor interaction was investigated. The receptor protein, prepared from rat gastric epithelial cell membrane by affinity chromatography on laminin-coupled Sepharose, was radioiodinated, and incorporated into liposomes which exhibited specific affinity towards laminin-coated surface. The binding was inhibited by H. pylori lipopolysaccharide, which caused a maximum inhibition of 96% at 50 micrograms/ml. The inhibitory effect of the lipopolysaccharide was prevented by an antiulcer agent, ebrotidine that evoked essentially complete restoration in binding at 6-8 micrograms/ml. The results demonstrate that H. pylori through its lipopolysaccharide interferes with gastric epithelial cell-laminin binding, and that this disruptive effect could be successfully countered by ebrotidine.


Avian paramyxovirus type 1 infections in racing pigeons in California. I. Clinical signs, pathology, and serology.

An outbreak of diarrhea and neurological disease in California racing pigeons caused by avian paramyxovirus type 1 (PMV-1) is documented. Predominant clinical signs were polydipsia, ataxia, poor balance, torticollis, head tremors, inability to fly, and diarrhea that was unresponsive to therapy. Gross pathologic findings were often unremarkable or non-specific. The predominant histologic lesions were interstitial nephritis, chronic tubular necrosis, lymphoplasmacytic infiltration within the kidney, liver, and pancreas, and focal non-suppurative encephalitis. Pigeons from 20 submissions demonstrated characteristic clinical signs of PMV-1 infection. Pigeons from 17 submissions exhibited typical histopathology. Serologic evidence of PMV-1 infection was present in pigeons from 13 submissions, and PMV-1 was isolated from pigeons received in six submissions. None of these pigeons had been vaccinated against PMV-1.


Atrial natriuretic factor concentrations during pregnancy and in the postpartum period.

Atrial natriuretic factor (ANF) is a hormone that regulates fluid and electrolyte homeostasis. Increased intra-atrial pressure or atrial distention, which might occur secondary to intravascular volume expansion, stimulate the secretion of ANF by human atrial myocytes. During normal human pregnancy, there is a progressive increase in total intravascular fluid volume. Thus, we asked the following question: Does this physiologic adaptation to pregnancy result in an increase in ANF concentrations? Concentrations of alpha-human ANF (alpha-hANF) were measured by a specific radioimmunoassay in venous blood samples obtained longitudinally in the first, second, and third trimesters of pregnancy, during the intrapartum period, in the early postpartum period, and 6 to 8 weeks postpartum from 11 normal women who had no antepartum, intrapartum, or postpartum complications. Maternal circulating alpha-hANF levels were not different from those seen in the nonpregnant state. However, higher alpha-hANF concentrations were noted in the early postpartum period. Although the hypervolemia of normal pregnancy is not associated with higher alpha-hANF concentrations, other possibilities (such as increased ANF clearance, dilutional effects) need to be investigated. Finally, the etiology for the transient increase in alpha-hANF levels in the early postpartum period remains to be elucidated.


Biological properties of interleukin 10.

An enormous amount of information on interleukin 10 (IL-10) has been gathered since its original description as cytokine synthesis inhibition factor (CSIF) several years ago. In this short article, Maureen Howard and Anne O'Garra summarize what is currently known of the biological properties of IL-10 and speculate on its clinical potential.


Regulation of alpha 1-antitrypsin synthesis by granulocyte macrophage colony-stimulating factor in the U937 promonocytic cell line.

Undifferentiated U937 cells possess low numbers (approximately 1,100 per cell) of receptors for granulocyte macrophage colony-stimulating factor (GMCSF). The receptors present are of at least two types with different affinities. A small number (less than 200 per cell) are of higher affinity (approximate Kd 97pM), and a larger number (approximately 900 per cell) are of lower affinity (approximate Kd 680pM). Following differentiation with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (PMA), the differentiated cells express a reduced number of receptors (approximately 680 per cell). These receptors are present as a single class with an approximate affinity of 230pM (Kd). The undifferentiated cells were responsive to GMCSF and this cytokine caused a seven-fold increase in accumulation of alpha 1-antitrypsin (alpha 1AT) compared to the control cells. This was accompanied by a similar increase in alpha 1ATmRNA, which suggests that the rate of alpha 1AT accumulation was regulated at the transcriptional level. After differentiation with PMA, alpha 1AT accumulation was not influenced by GMCSF, although the cells continued to bind the cytokine. These results imply that U937 cells do respond to GMCSF and this event involves binding of the ligand to a small number of specific cell surface receptors only present in the undifferentiated cells. Furthermore the response of these cells (in terms of alpha 1AT production) is associated with the type of GMCSF receptors expressed.


WY 18,251 (Tilomisole), an analog of levamisole: tolerability, and immune modulating effects in cancer patients.

Wy 18,251 (Tilomisole; Wyeth Laboratories, Philadelphia, PA, USA) is a benzimidazole that is structurally similar to the antihelminth levamisole that has recently been approved for the adjuvant treatment of colon cancer. In preclinical models, Tilomisole caused less agranulocytosis than levamisole, but retained immunomodulating capabilities. We examined the effects of Tilomisole administered to cancer patients in four different dose schedules: 60 mg/m2 orally (p.o.) weekly, and 60, 300, or 960 mg/m2 p.o. daily for 1 month. All patients were immunosuppressed when treatment was initiated as defined by standardized assays of phytohemagglutinin, concanavalin A, pokeweed mitogen, and mixed lymphocyte responses. Tilomisole was well tolerated with no significant side effects in 25 patients. There were no antitumor responses noted in this setting of metastatic cancer. There was no improvement in concanavalin A or pokeweed mitogen assays at any dose or schedule, but there was sustained improvement in mixed lymphocyte reaction and phytohemagglutinin assays at the 60 mg/m2 daily dose. This drug may have favorable biological response modifying effects in vivo and be a suitable alternative to levamisole in cancer treatment, especially if agranulocytosis is a significant problem associated with widespread use of levamisole.


Production of hybrid bispecific antibody recognizing human colorectal carcinoma and CD3 antigen.

The present study reports on the use of gene transfer by vector DNA in the generation of hybrid hybridoma, the quadroma secreting the hybrid bispecific antibody. A quadroma B72.3neo/OKT3gpt was simply derived from the fusion of two hybridoma cell lines, B72.3 and OKT3, tagged with vector DNA mpSV2neo and mpSV2gpt, respectively, and selected in the media containing both G418 and mycophenolic acid. The hybrid bispecific antibody B72.3/OKT3 was purified from the quadroma ascites by the use of hydroxylapatite column on high-pressure liquid chromatography. This bispecific antibody contained one binding site for the TAG72 antigen on OVCAR3 tumor cells and the other binding site for the CD3 molecule on human T cells. It was able to target human T lymphocytes to significantly lyse the human ovarian cancer cells and may therefore be useful in immunotherapy of cancer.


Providing care to persons with physical disability. Effect on family caregivers.

Studies on caregiving often assume that outcomes will be problematic and assess negative factors, such as burden or stress. Results may be biased by detailing only the problems encountered. The current study assessed positive, neutral and negative aspects of caregiving and evaluated the impact of caregiving using criteria based on an accepted model of family functioning. Of 942 consecutive hospital admissions, 217 subjects required assistance in personal care and returned home with a primary caregiver. Caregivers reported moderately more anxious, depressive and somatic symptoms than expected from standardized tests, but these findings were not clinically or statistically significant. Family functioning was related to the duration of the caregiving experience. Family relations seemed to be a source of strength for caregivers, regardless of disability type. Further research is needed to determine if family functioning can be used to buffer against unfavorable aspects of caregiving or to enhance positive aspects of the situation.


Functional outcome in children with traumatic brain injury. Agreement between clinical judgment and the functional independence measure.

As improvements in the delivery of trauma care have increased survival from injury, it has become essential to assess the resulting morbidity to plan for medical and psychosocial services, particularly for children whose needs may be wide and long term. This paper focuses on the assessment of disability of 598 children, age 8 to 19 yr, hospitalized for traumatic brain injury with or without injury to other body regions, exclusive of spinal cord injury. The disability was measured at discharge from acute care in nine areas of functional activities and a recovery time assigned by a clinician. For the study, children were divided into three groups: those whose recovery was expected in less than 7 months (Group A: n = 463), in 7 to 24 months (Group B: n = 66) and in greater than 2 yr (Group C: n = 69). The clinician's expectation of recovery time significantly (P less than 0.01) reflected the injury severity as measured by the Glasgow Coma Scale and the Injury Severity Score. By the Glasgow Coma Scale, 16.4% were comatose on admission in Group A, 51.5% in Group B and 58% in Group C. The Injury Severity Score was significantly different with 25.5% severely injured in Group A, 68.2% in Group B and 84% in Group C. At discharge, 15% in Group A had four or more areas of impairments, 61% in Group B and 84% in Group C. The Functional Independence Measure confirmed the clinician's assessment of compromise with significantly (P less than 0.01) different average values of 110, 80 and 58 for Groups A, B and C, respectively.


Rehabilitation in adults with human immunodeficiency virus-related diseases.

The acquired immunodeficiency syndrome is a fatal disorder of cell-mediated immunity caused by the human immunodeficiency virus (HIV). As many as one million Americans infected with HIV can expect improved survival with more advanced treatment approaches. Complications of HIV infection occur in the brain, spinal cord, muscle, nerve, joints and other organ systems, which lead to extensive impairments. As survival increases, rehabilitation professionals can anticipate a greater number of referrals for the assessment and management of physical disability in persons with HIV infection. This article reviews HIV-related disease, impairment, disability and handicap pertinent to rehabilitation medicine. An agenda for future research is also proposed. Current knowledge and models or rehabilitation care can be applied to HIV-related physical disability in an effort to improve overall quality of life.


Endothelin peptides: biological activities, cellular signalling and clinical significance.

Endothelins (ET-1, ET-2 and ET-3) are a family of 21 amino acid peptides produced by endothelial cells. They are thought to regulate the local vasomotor tone with endothelium-derived relaxing factors. ETs are the most potent vasoconstrictor substances yet identified and veins and renal vasculature are the most sensitive targets. They reduce cardiac output and have positive inotropic and chronotropic effects. ETs increase the secretion of atrial natriuretic peptide (ANP), aldosterone and catecholamines but reduce renal blood flow and glomerular filtration and they also have mitogenic properties. ETs bind to receptors (ETA and ETB), activate phospholipase C, modulate intracellular Ca2+ concentration and open Ca2+ channels. Vasoactive agents (adrenaline, angiotensin, vasopressin, thrombin, endotoxins) and hypoxia stimulate the release of ET and also ET gene expression. Raised concentrations of plasma ET have been found to occur in several clinical conditions such as hypertension, myocardial infarction, cardiogenic shock, pregnancy induced hypertension, arteriosclerosis, Raynaud's disease, subarachnoid haemorrhage, uraemia, ulcerative colitis, Crohn's disease and surgical operations suggesting that ETs have a role in several patophysiological processes.