Treatment of chronic myeloid leukemia with allogeneic bone marrow transplantation after preparation with BuCy2. One hundred fifteen patients with chronic myelocytic leukemia (CML) were administered busulphan 4 mg/kg for 4 days and cyclophosphamide 60 mg/kg on each of 2 days (BuCy2) followed by allogeneic bone marrow transplantation from histocompatible sibling donors. For 62 patients in chronic phase, 26 in accelerated phase, and 27 in blast transformation, the actuarial survival at 3 years was 58%, 41%, and 25%, respectively. Actuarial probability of relapse was 3%, 12%, and 27%, respectively. Only two patients in chronic phase showed a transient cytogenetic relapse and one of these died from subsequent transplant-related complications, whereas the other remains cytogenetically normal 697 days posttransplant. Patients who were transplanted within 1 year of diagnosis in chronic phase had a survival of 70% compared with 40% when transplanted beyond 1 year from diagnosis. This significant difference in survival was due to transplant-related complications and was correlated with previous exposure to high doses of busulphan. This study indicates that BuCy2 is a useful conditioning regimen for marrow transplantation in patients with CML and results in similar survival statistics and transplant-related mortality as would be expected with conditioning regimens containing total body irradiation. It is possible that relapse after BuCy2 may be lower than expected with regimens containing total body irradiation, but larger analyses are required.


Human breast cancer: survival from first metastasis. Breast Cancer Study Group. Survival from the detection of first metastasis (SAM) was analyzed in a single center series of 258 patients with advanced breast cancer. During the 15 year period covered by this study 230 patients died, 215 of their disease. The overall median SAM was 28 months. Univariate analysis of SAM stratified by first dominant site of metastasis, estrogen receptor status (ER), progesterone receptor status (PgR), tumor size, axillary lymph node status, patient age, menopausal status, and disease-free interval (DFI) showed the first dominant site of metastasis, ER, PgR, and axillary lymph node status to be significantly associated with SAM. Patients with visceral metastasis as first dominant site of metastasis had significantly shorter survival than those with either bone or soft tissue metastasis, median SAM 16 vs. 34 vs. 41 months respectively (P less than 0.001). SAM also differed according to the steroid hormone receptor status of the primary tumor: median SAM 34 and 33 months for patients with ER-positive or patients with PgR-positive tumors against 14 months for patients with ER-negative or with PgR-negative tumors (P less than 0.001). Patients with axillary lymph node involvement at primary disease had a shorter SAM than those without, median SAM 24 vs. 35 months (P = 0.006). No association between SAM and either tumor size, patient age, menopausal status, or DFI could be observed. Multivariate analysis including first dominant site of metastasis, ER, PgR, and axillary lymph node status showed the first dominant site of metastasis, ER, and axillary lymph node status to be independently associated with SAM.


Prognostic significance of the immunohistochemical reaction to human milk fat globule antibodies in node-negative and node-positive breast cancer. The status of axillary lymph nodes in patients with breast cancer is important prognostically but does not identify all patients who will have long or short survival. To determine if the immunohistochemical reaction of tumor cells to human milk fat globule (HMFG) antibodies will define prognosis more specifically, we examined patients with node-negative disease and patients with more than three positive nodes, the extremes of the prognostic spectrum. In both node-negative and node-positive groups, patients who relapsed were matched by age at diagnosis, tumor size, histologic type, and receptor status, with patients who remained disease-free for a minimum of 48 months. Patients with poor survival had a higher proportion of poorly differentiated cancers. The ability to generate antigens recognized by HMFG antibodies was decreased in patients with recurrent disease, but this was significant only in patients with node-positive tumors. Tumors of patients who remained disease-free were more likely to have a pattern of membrane staining, while cytoplasmic staining was more frequent in those who relapsed. The results suggest that immunohistologic response to HMFG antibodies may assist in identifying cancers with poor prognosis, supplementing the prediction derived from node status.


Epithelial membrane antigen expression in breast fluids and 'witch's milk'. We have examined breast fluids from non-lactating women and male neonates for the expression of epithelial membrane antigen (EMA), also termed polymorphic epithelial mucin (PEM). All fluids exhibited significant amounts of EMA as demonstrated by immunoblot analyses and enzyme immunoassay. EMA was present in the breast fluids of both pre- and post-menopausal women, and these results suggest that nipple aspirates could provide an easily accessible source of antigen for assessing the value of EMA as a tumor marker both before and after various therapeutic modalities. The presence of EMA in the 'witch's milks' indicates that full maturation of the breast is not a prerequisite for antigen expression in breast tissue.


The value of clinical assessment in the diagnosis of icterus and cholestasis. We studied the reliability of the clinical assessment and the discriminatory value of different symptoms and signs in diagnosing obstructive and non-obstructive diseases causing icterus and/or cholestasis. During a period of two-and-a-half years, clinical assessment done by both physicians-in-training and by senior physicians was completed for 266 patients, and the usefulness of different symptoms and signs was tested in 220 of these. Clinical assessment was found to be a reliable method in distinguishing between obstructive and non-obstructive conditions causing icterus, with the sensitivity of 92% and specificity of 86%. In cases of anicteric cholestasis, the sensitivity and specificity of clinical assessment were 74% and 80%, respectively. Abdominal pain and abdominal tenderness were significantly (p less than 0.01) associated with obstructive diseases, whereas an enlarged liver, fever and excessive consumption of alcohol were associated with non-obstructive diseases (p less than 0.01, p less than 0.05, p less than 0.05, respectively). Itching, vomiting, intolerance to fatty foods, previous cholecystectomy, abdominal tumour and clinical icterus had no discriminatory value. Clinical evaluation is a reliable method in the diagnostic workup of a patient with icterus or anicteric cholestasis, and it is still of crucial importance in directing further investigations.


Endoscopy to detect oral and oesophageal candidiasis in acquired immune deficiency syndrome. Cytologic evidence of candidiasis was sought on endoscopic oesophageal brushings from 116 patients with acquired immune deficiency syndrome (AIDS) to determine the reliability of oesophagoscopy and the possibility of predicting Candida spp. oesophagitis from concomitant oral candidiasis or oesophageal symptoms. Oesophageal candidiasis was present in 42 patients and constituted the first opportunistic infection in 19 patients. Sensitivity and specificity were, respectively, 98% and 96% for oesophagoscopy, 69% and 42% for oral candidiasis, 52% and 74% for oesophageal symptoms, and 83% and 35% for the presence of at least one of these last two parameters. Endoscopy also proved to be the examination of choice for diagnosis, and cytology was needed only when it was negative. Oral candidiasis and oesophageal symptoms were not sufficient to predict oesophageal candidiasis. Endoscopy would seem to be indispensable to the diagnosis of oesophageal candidiasis and its differentiation from other forms, thus preventing any empirical resort to unwarranted forms of treatment. It is also indicated for staging purposes in asymptomatic patients, since oesophageal candidiasis is one indicator of the transition to full-blown AIDS.


Androgen profile in patients with pancreatic carcinoma. Serum testosterone, free testosterone and androstenedione levels were measured in 28 male patients with pancreatic cancer and compared with the values obtained from 28 male patients with chronic pancreatitis, 29 with gastrointestinal malignancies and 41 healthy controls. Mean total testosterone values were significantly lower in the pancreatic cancer group when compared to chronic pancreatitis and healthy controls. Total testosterone concentrations were also significantly lower in patients with gastrointestinal malignancies when compared to healthy controls. No difference was found in free testosterone and androstenedione levels in the four groups of patients. Total testosterone serum levels correlated significantly with poor nutritional status. This study confirms low testosterone levels in patients with pancreatic cancer, but provides no evidence to support a direct relationship between pancreatic cancer and testosterone metabolism.


The theophylline disposition after caffeine administration in liver cirrhosis: an index of liver function. Six blood samples covering a 24 hr post caffeine dosage were drawn in 8 healthy subjects and 18 patients with liver cirrhosis. Caffeine and theophylline concentration were assayed by gas-chromatography and fluorescent polarization immunoassay, respectively. In normals the maximum theophylline levels were found between 3 and 8 hrs (62.5% at 8 hrs) and ranged 50-420 ng/ml, whereas these levels in cirrhotic patients were noted between 3 and 12 hrs (61.1% at 8 hrs) and ranged 40-670 ng/ml. The largest difference in mean theophylline concentration between normals and cirrhotics was found at 6 hrs (348 +/- 103.7 ng/ml vs 217.1 +/- 140.8 ng/ml; p less than 0.02) and 24 hrs (101.6 +/- 57.3 ng/ml vs 172.2 +/- 119.6 ng/ml; p = 0.075) after caffeine dosing. Theophylline formation rate (theo6) differentiated controls from cirrhotics in the initial stage of the disease (Child-Pugh A), however it failed to discriminate between initial and late cirrhosis. In contrast, the ability of liver to remove theophylline (theo24) differentiated effectively these groups of patients. Theo6 to theo24 ratio was a valuable index of liver function, although its capacity to detect early cirrhosis was unsatisfactory.


Treatment of erosive reflux oesophagitis: a double-blind multicentre trial with nizatidine 300 mg b.i.d. versus placebo. Histamine H2-receptor antagonists at conventional doses have proved only partly efficacious in the treatment of reflux oesophagitis. The aim of this study, therefore, was to compare the efficacy of high doses of nizatidine (300 mg b.i.d.) versus placebo in 117 patients with grade I and II oesophagitis. After 6 weeks' treatment, 70.6% of nizatidine-treated patients showed complete endoscopic healing against 25.4% of placebo-treated subjects (p less than 0.001). After 12 weeks, the respective healing rates were 77.5% and 47.4% (p less than 0.01). Nizatidine also proved significantly more effective than placebo in improving overall symptoms (p less than 0.05). Antacid intake was significantly greater in the placebo group (p less than 0.001). Both treatments were well tolerated. In conclusion, this study demonstrates that nizatidine at the dose of 300 mg b.i.d. for 6-12 weeks constitutes an effective treatment for patients with reflux oesophagitis.


The prevalence of gallstones in patients suffering from liver cirrhosis: a clinico-statistical study of 350 patients. The overall prevalence according to sex and to age group of biliary calculosis was assessed in 350 patients with liver cirrhosis: data were compared with homogeneous findings in the general population of the GREPCO study. Cholelithiasis was found to be significantly more frequent in cirrhotics, and the pattern was confirmed when data were analyzed according to sex; a significantly higher percentage was found in cirrhotics of the 40-49 and 60-69 age groups. Among cirrhotics with gallstones, alcoholics represented a smaller percentage compared to non-lithiasic cirrhotics. The incidence of complications such as digestive hemorrhage, coma, and hepato-renal syndrome, was equal in cirrhotics with and without biliary calculosis, or, as far as coma was concerned, even lower among the former. A fatal outcome was less frequent in cirrhotic patients with than in those without cholelithiasis. Our results go to show that biliary calculosis does not aggravate the course of liver cirrhosis.


Neurotensin: a physiological regulator of exocrine pancreatic secretion? The aim of the present review was to evaluate the effects of neurotensin on the exocrine pancreatic secretion. Neurotensin immunoreactivity has been identified in the central nervous system and also in the digestive system, where it is found in specific endocrine cells of the intestinal mucosa (N cells), in nerve fibers of the enteric nervous system and in intrapancreatic ganglia (both in nerves and cell bodies). Studies in laboratory animals and in humans have demonstrated that the ingestion of a meal causes a significant release of neurotensin into the circulation and that exogenous administration of low doses of the peptide strongly stimulates exocrine pancreatic secretion. These findings, together with the demonstration that the immunoneutralization of circulating neurotensin significantly reduces the pancreatic secretory response to a meal, suggest that neurotensin is a physiological regulator of exocrine pancreatic secretion.


Subclinical coeliac disease.

Subclinical coeliac disease. The prevalence of coeliac disease (CD) was investigated in an epidemiological study of school children from a district of Rome. Mass screening of IgA-AGA levels (anti-gliadin antibody) were determined in blood samples from the study group and the results were positive in 19 children. Eighteen of these agreed to undergo endoscopic biopsy. Histological study of the duodenal specimens revealed villous atrophy in twelve children none of whom had the characteristic symptoms of CD. The most frequent complaints were abdominal pain, aphtous stomatitis, and atopic dermatitis. The high prevalence of CD in this study suggests the necessity for the widest range of epidemiological research.


Morphology of the adrenal homologues in two hillstream teleostean fishes from India. In Garra gotyla and Pseudecheneis sulcatus, the interrenal and chromaffin tissues represent homologues of the adrenal cortex and medulla, respectively, and are confined to the largely lymphoid head kidneys in a bilaterally symmetrical topographical pattern. Together they form a collar round the postcardinal vein, with a thickness of 300 microns in Garra gotyla and 150 microns in Pseudecheneis sulcatus. Distributionally, the interrenal tissue conforms to Nandi's type III and type I and the chromaffin tissue to type V and type III in Garra gotyla and Pseudecheneis sulcatus, respectively. The interrenal cells in these species are polygonal, cuboidal or columnar, and are filled with coarse basophilic cytoplasm. The chromaffin cells form syncytial patches and have sparsely granular cytoplasm.


A new explanation of the cancellous bone architecture. Various objections can be made to all the theories so far put forward in explanation of the architecture of cancellous bone. The author suggests another explanation, which takes into account the following points: 1) the structure of the secondary spongiosa is based on the pre-existent primary spongiosa, 2) the secondary spongiosa develops under alternating pressures from different directions, 3) oblique forces from marginal directions corresponding to extreme positions on the joint place the greatest strain on the spongiosa trabeculae, as demonstrated by means of a geometrical model. Oblique forces are therefore of decisive morphogenetic importance. 4) The spongiosa trabeculae are oriented in the direction of the oblique marginal forces, in accordance with the experimentally demonstrated mechanism of the strain-dependent reaction of the bone. Spatially, the secondary spongiosa assumes a fan-shaped structure. Two-dimensionally, the two intersecting systems are compression systems, each of which depends on another marginal loading direction. This pattern offers an optimum solution to the problem of the transmission of alternating forces to the diaphysis from various directions, using a minimum of material.


Origin of the v. portae and variability of its tributaries in laboratory animals. VI. The laboratory mouse (Mus musculus var. alba). The authors studied the origin and variability of the tributaries of the v. portae in 30 adult laboratory mice (Mus musculus var. alba) of both sexes, after first injecting the portal bed with bluedyed latex. In 19 cases (63.3%) the v. portae was formed by the union of three tributaries and in 11 cases (36.7%) by the union of four to eight. The v. mesenterica cranialis was a constant tributary in every case (100%). The v. lieanalis was a tributary in 27 cases (90.0%) and the next most frequent tributary was the v. pancreaticoduodenalis (14 cases--46.7%) A v. gastrica sinistra was found in every case (100.0%), in 24 cases (80.0%) it joined the v. lienalis and in the other six (20.0%) it was a direct tributary of the v. portae. A v. cardiaca was also observed in every case (100%). In 28 cases (93.3%) it was a tributary of the v. gastrica sinistra and in the remaining two (6.7%) it was a direct tributary of the v. portae. A v. pylorica was found in 27 mice (90.0%). Most often it was a tributary of the v. gastroepiploica dextra (11 cases--36.7%) or the v. gastrica sinistra (9 cases--30.0%). In only one case was it a direct tributary of the v. portae. A v. pancreaticoduodenalis cranialis was present in a total of 28 cases (93.3%). In 12 cases (40.0%) of already originated in the region of the cauda pancreatis and in 16 cases (53.3%) it arose only from the corpus and caput pancreatis.(ABSTRACT TRUNCATED AT 250 WORDS)


Expression of a viral avirulence gene in transgenic plants is sufficient to induce the hypersensitive defense reaction. Tobacco plants containing the N' resistance gene exhibit a hypersensitive defense reaction when infected with tomato mosaic virus (ToMV); infection results in necrotic lesions at the primary infection sites. In an attempt to investigate the molecular mechanism(s) underlying this plant-pathogen interaction, the ToMV coat protein gene was joined by a transcriptional fusion to the strong constitutive 35S RNA promoter from cauliflower mosaic virus. This chimeric gene was introduced via Agrobacterium-mediated transformation into isogenic tobacco cultivars differing only with respect to the N' gene. Strong necrotic reactions were observed on most emerging calli of the N' genotype, but never on calli lacking the N' resistance gene. These data indicate that the coat protein of ToMV is, on its own, sufficient to induce a hypersensitive reaction in tobacco. Thus, recognition of a single viral gene product may be the only prerequisite for the induction of a specific defense reaction in higher plants.


The effect of methotrexate (MTX) on the small intestine of the mouse. III. Mitochondria and succinic dehydrogenase (SDH). The effect of the cytotoxic agent MTX on the mitochondrial content and on SDH activity in the jejunal mucosa of mice was studied. The control epithelium contained variable quantities of mitochondria, in the form of granules, short rods and filaments. In the crypt cells these organelles were larger than in the villus cells. The concentration of mitochondria close to the brush border and the basement membrane is indicative of their importance in production of the energy needed for active transport across the plasma membrane. After MTX treatment, there was a general decrease in the number, size and stainability of the mitochondria. In the control, SDH activity was moderate and its localization coincided topographically with the distribution of the mitochondria. The decrease in SDH activity after MTX, correlated to the decrease in the mitochondrial content, might be due to mitochondrial damage resulting form the indirect effect of MTX.


Regulation of enzymes involved in lignin biosynthesis: induction of O-methyltransferase mRNAs during the hypersensitive reaction of tobacco to tobacco mosaic virus. The mRNAs encoding orthodiphenol-O-methyltransferases (OMTs; EC 2.1.1.6), which are involved in the biosynthesis of lignin precursors, are highly induced in tobacco leaves during the hypersensitive reaction to tobacco mosaic virus (TMV). OMT messengers were fractionated on a sucrose gradient and translated in vitro. Protein A-Sepharose columns adsorbed with specific antisera raised against purified OMTs were used to select translation products, and the translatable activity of OMT mRNA was measured at different stages of infection. Oligonucleotides derived from peptide sequences of purified OMT I were used to prime polymerase chain reactions; total RNA was used as template to allow the isolation of an OMT I clone. RNA blots, hybridized with the OMT I probe, revealed a unique messenger of 1.7 kb. The kinetics of accumulation of OMT I mRNAs during the hypersensitive reaction to TMV parallels the kinetics of translation and suggests that an increase in mRNA controls the increase in the rate of enzyme synthesis. In healthy plants, RNA blot hybridization showed that the steady-state level of OMT I mRNA is very high in vascular tissue compared to the level measured in leaves.


Analysis of DNA sequences transcribed at high levels in Bradyrhizobium japonicum bacteroids but not necessary for symbiotic effectiveness. Five regions of the Bradyrhizobium japonicum genome, which are transcribed at high levels in nitrogen-fixing soybean (Glycine max) nodules, were identified. None of these regions contained previously identified genes (e.g., nif, nod, and fix genes) that are known to be essential for development of functional nitrogen-fixing nodules. To assess the role of these regions in the development of the B. japonicum-soybean symbiosis, we cloned and used them to construct B. japonicum strains, in which large DNA segments (2.0-6.8 kilobases) containing the highly transcribed regions were deleted. The deletion strains were examined for symbiotic effectiveness and were found to be indistinguishable from the wild-type strain. Transcription of the cloned regions under a variety of physiological conditions and in several defined mutant B. japonicum strains was also examined. The transcriptional start sites for one pair of divergent transcripts were determined; the promoters do not contain any of the conserved sequences found in B. japonicum genes involved in symbiosis or nitrogen metabolism.


Ultrastructure of rabbit tracheal epithelium after the administration of Hexabrix--a hexaiodated contrast agent for tracheobronchography. The ultrastructure of the tracheal epithelium after the application of 1 ml of Hexabrix (a hexaiodated contrast agent for tracheobronchography) into the airways was studied. Severely altered pseudostratified columnar epithelium was found in the trachea. Eighty-one +/- 5% of the goblet cells had been stimulated to discharged mucus. Forty-three +/- 3% of them were completely exhausted and had degenerated. The ciliated cells displayed marked signs of pathological alteration up to vacuolar degeneration. The ciliary border above the epithelium was severely damaged. The mean number of cilia per micron 2 fell to 3.3 +/- 0.5, but the proportion of intact cilia did not drop below 95%. As morphological signs of impaired self-cleaning ability of the airway epithelium, a large amount of inspissated mucus and numerous bacteria were found in the area of the impaired ciliary border. Coarse grained contrast substance of supreme electron density was intermingled with the condensed mucus. The most pronounced damage to the cells was observed at the sites of direct contact of the contrast agent with the cell membranes.


Identification of a lysA-like gene required for tabtoxin biosynthesis and pathogenicity in Pseudomonas syringae pv. tabaci strain PTBR2.024. Pseudomonas syringae pv. tabaci strain PTBR2.024 produces tabtoxin and causes wildfire disease on tobacco and green bean. PTBR7.000, a Tn5 mutant of PTBR2.024, does not produce tabtoxin, is nonpathogenic on tobacco, and is prototrophic. A 3-kb fragment from a genomic library of the parent strain PTBR2.024 complemented both mutant phenotypes. This 3-kb fragment contains two open reading frames (ORFs), ORF1 and ORF2, and two truncated ORFs, ORF3 and ORF4. The Tn5 insert in PTBR7.000 was mapped to ORF2, and complementation studies showed that an intact ORF2 was sufficient to restore tabtoxin production and pathogenicity. The deduced amino acid sequences of ORF2 and truncated ORF3 contain significant homology to bacterial lysine biosynthetic enzymes, diaminopimelate decarboxylase, and delta 1-piperidine-2,6-dicarboxylate succinyl transferase, respectively. ORF2, however, is not required for lysine biosynthesis. We designated the sequence corresponding to ORF2 as gene tabA and propose that the product of tabA is an enzyme in the tabtoxin biosynthetic pathway that recognizes a substrate analogue of a compound in the lysine biosynthetic pathway.


The a and b loci of Ustilago maydis hybridize with DNA sequences from other smut fungi. The smut fungi are obligately parasitic during the sexual phase of their life cycle, and the mating-type genes of these fungi play key roles in both sexual development and pathogenicity. Among species of smut fungi it is common to find a bipolar mating system in which one locus with two alternate alleles is believed to control cell fusion and establishment of the infectious cell type. Alternatively, several species have a tetrapolar mating system in which two different genetic loci, one of which has multiple alleles, control fusion and subsequent development of the infection hyphae. Cloned sequences from the a and b mating-type loci of the tetrapolar smut fungus Ustilago maydis were used as hybridization probes to DNAs from 23 different fungal strains, including smut fungi with both tetrapolar and bipolar mating systems. In general, all of the smut fungi hybridized with the mating-type genes from U. maydis, suggesting conservation of the sequences involved in mating interactions. A selection of DNAs from other ascomycete and basidiomycete fungi failed to hybridize with the U. maydis mating-type sequences. Exceptions to this finding include hybridization of DNA from the a1 idiomorph of U. maydis to DNA from one strain of U. violacea and hybridization of both a idiomorphs to DNA from Saccharomyces cerevisiae.


A gene encoding a protein with seven zinc finger domains acts on the sexual differentiation pathways of Schizosaccharomyces pombe. Byr3 was selected as a multicopy suppressor of the sporulation defects of diploid Schizosaccharomyces pombe cells that lack ras1. Like cells mutant at byr1 and byr2, two genes that encode putative protein kinases and that in multiple copies are also suppressors of the sporulation defects of ras1 null diploid cells, cells mutant at byr3 are viable but defective in conjugation. Nucleic acid sequence indicates byr3 has the capacity to encode a protein with seven zinc finger binding domains, similar in structure to the cellular nucleic acid binding protein (CNBP), a human protein that was identified on the basis of its ability to bind DNA. Expression of CNBP in yeast can partially suppress conjugation defects of cells lacking byr3.


In vivo import of firefly luciferase into the glycosomes of Trypanosoma brucei and mutational analysis of the C-terminal targeting signal. The compartmentalization of glycolytic enzymes into specialized organelles, the glycosomes, allows the bloodstream form of Trypanosoma brucei to rely solely on glycolysis for its energy production. The biogenesis of glycosomes in these parasites has been studied intensively as a potential target for chemotherapy. We have adapted the recently developed methods for stable transformation of T. brucei to the in vivo analysis of glycosomal protein import. Firefly luciferase, a peroxisomal protein in the lantern of the insect, was expressed in stable transformants of the procyclic form of T. brucei, where it was found to accumulate inside the glycosomes. Mutational analysis of the peroxisomal targeting signal serine-lysine-leucine (SKL) located at the C-terminus of luciferase showed that replacement of the serine residue (Serine548) with a small neutral amino acid (A, C, G, H, N, P, T) still resulted in an import efficiency of 50-100% of the wild-type luciferase. Lysine549 could be substituted with an amino acid capable of hydrogen bonding (H, M, N, Q, R, S), whereas the C-terminal leucine550 could be replaced with a subset of hydrophobic amino acids (I, M, Y). Thus, a peroxisome-like C-terminal SKL-dependent targeting mechanism may function in T. brucei to import luciferase into the glycosomes. However, a few significant differences exist between the glycosomal targeting signals identified here and the tripeptide sequences that direct proteins to mammalian or yeast peroxisomes.


A low copy number central sequence with strict symmetry and unusual chromatin structure in fission yeast centromere. Fission yeast centromeres vary in size but are organized in a similar fashion. Each consists of two distinct domains, namely, the approximately 15-kilobase (kb) central region (cnt+imr), containing chromosome-specific low copy number sequences, and 20- to 100-kb outer surrounding sequences (otr) with highly repetitive motifs common to all centromeres. The central region consists of an inner asymmetric sequence flanked by inverted repeats that exhibit strict identity with each other. Nucleotide changes in the left repeat are always accompanied with the same changes in the right. The chromatin structure of the central region is unusual. A nucleosomal nuclease digestion pattern formed on unstable plasmids but not on stable chromosome. DNase I hypersensitive sites correlate with the location of tRNA genes in the central region. Autonomously replicating sequences are also present in the central region. The behavior of truncated minichromosomes suggested that the central region is essential, but not sufficient, to confer transmission stability. A portion of the outer repetitive region is also required. A larger outer region is necessary to ensure correct meiotic behavior. Fluorescence in situ hybridization identified individual cens. In the interphase, they cluster near the nuclear periphery. The central sequence (cnt+imr) may play a role in positioning individual chromosomes within the nucleus, whereas the outer regions (otr) may interact with each other to form the higher-order complex structure.


The physician in aviation.

The physician in aviation. As the human body was introduced to flight and its unfamiliar, hostile atmospheric environment, the medical profession had to become familiar with its effects in order to develop preventive measures. In this way, the field of aerospace medicine had its origin.


Motor vehicle fatalities in Rhode Island (FY1990-1991): a report on driver impairment. Autopsy specimens from 52 fatally injured drivers in Rhode Island were analyzed for the presence of alcohol and other drugs of abuse, including, among others, cocaine, opiates, cannabinoids (THC), and phencyclidine (PCP). The ages of the drivers ranged from 16 to 87 years; 41 were male and 11 female. Based on this sample, 65% of Rhode Island driver fatalities involve drugs. The most common drug, alcohol was found in 59% of the cases. Drugs other than alcohol were detected in 19% of the cases, 13% had illicit drugs found in combination with alcohol, and 6% had illicit drugs only.


Affordability considerations in certificate-of-need hospital capital expenditure review determinations. Beginning in 1984, public affordability became a central standard along with public need in the review of hospital proposals for capital development in Rhode Island's certificate-of-need (CON) program.


Evaluation of autonomic function.

Evaluation of autonomic function. Clinical laboratory evaluation of adrenergic function is lacking in sensitivity. Recent studies suggest that components of the Valsalva maneuver can be used to evaluate adrenergic function. Late phase II and phase IV are primary regulated by peripheral and cardiac sympathetic activity, respectively. With progressive adrenergic failure there is a loss of IIl, an increase in IIe and a loss of IV in that order. Baroreflex gain can be described by the heart period/blood pressure (BP) response. An alternative approach of expressing latency instead of gain is of interest but is of uncertain validity. Evaluation of heart rate recordings in the frequency domain using power spectral analysis can be used to study parasympathetic/sympathetic balance in humans. Its value as a clinical test remains to be established. Prolonged tilt is a sensitive and probably specific test of vasodepressor syncope. Isoproterenol infusion during tilt is of doubtful specificity.


Aging and the autonomic nervous system.

Aging and the autonomic nervous system. Most studies show a decline in autonomic nervous system (ANS) function with advancing age. The occasional heterogenous responses of ANS to aging, however, suggest that psychosocial and physiologic factors alter aging of ANS function.


Autonomic involvement in systemic diseases. It is now well recognized that autonomic dysfunction may occur in disorders affecting the various body systems. Over the past year important observations have been reported in congestive cardiac failure, reflex sympathetic dystrophy (RSD), acquired immune deficiency syndrome (AIDS) and diabetes mellitus.


Autonomic dysfunction in central nervous system disorders. Dysautonomic symptoms are associated with many disorders of the central nervous system, in some of which the autonomic dysfunction is particularly conspicuous or the major cause of disability. New neuroimaging procedures and microneurographic techniques have helped to clarify the underlying pathophysiology and to distinguish or, classify disorders that are clinically similar. Recent studies also suggest that the autonomic nervous system is involved more frequently or extensively than previously thought in certain neurological conditions such as multiple sclerosis or human immunodeficiency virus (HIV) infection, and have helped to define the nature of its involvement in other disorders.


Treatment of autonomic failure.

Treatment of autonomic failure. The group of primary autonomic failure (AF) syndromes comprises pure AF (PAF), in which there are no central neurological signs, and multiple system atrophy (MSA) in which AF is accompanied by the overlapping degenerative disorders, striatonigral degeneration and olivopontocerebellar atrophy. Patients with these syndromes deteriorate progressively but, based on an understanding of the precise sites of the lesions, there are several ways of alleviating their deterioration, in particular the most disabling symptom, postural hypotension. The principles can be used in the treatment of AF in other general medical disorders, such as diabetes.


5-HT in nervous system disease and migraine. New developments defining the relationship between 5-hydroxytryptamine (5-HT; serotonin)1B and 5-HT1D receptors are reviewed and a novel pain control system involving spinal 5-HT3 receptors is described. The emerging roles of 5-HT receptor mechanisms in migraine and in the craving for alcohol are discussed.


Chemotherapy of gliomas.

Chemotherapy of gliomas. Gliomas are usually incurable with current treatment regimens. The mainstay of current therapy is surgery and radiotherapy. Adjuvant chemotherapy with nitrosourea-based regimens for high-grade glioma has now been established as a means of improving survival times, although the results are disappointing and the treatment may entail significant morbidity and does not offer the prospect of cure. The role of chemotherapy for low-grade glioma is controversial, and its possible role as a primary therapy aimed at delaying the need for radiotherapy in young children must be better defined. The literature regarding chemotherapy of glioma is reviewed with particular emphasis on recent publications.


Neoplastic disease of the spine.

Neoplastic disease of the spine. Spinal cord tumours continue to be a challenging clinical problem. Early diagnosis, especially with widespread use of magnetic resonance imaging (MRI), and advances in surgical technique enable a more aggressive approach to the management of these lesions.


Myelitis and toxic, inflammatory and infectious disorders. Developments in our understanding of the anatomical-clinical and pathological correlates of spinal cord disorders have greatly enhanced our understanding of the clinical presentation. The impact of viral disease on the spinal cord is reviewed. The value of magnetic resonance (MR) scanning of the brain and spinal cord in the evaluation, both in the short and long term, of patients with myelopathy is underlined.


Spinal cord injury.

Spinal cord injury. Continued investigation of the pathophysiology of primary and secondary neuronal injury following acute spinal cord injury (SCI) has led to positive results in two medical treatment protocols: methylprednisolone and GM1 ganglioside. The advent of improved high resolution radiologic studies has allowed a new dimension in the understanding of the physical and pathomechanical aspects of acute SCI. Advances in rehabilitation continue, allowing improved prognosis and long-term function. Prevention is clearly the best and most effective treatment of all.


Repair and regeneration: experimental aspects of spinal cord disease. Regeneration of spinal cord neurons after injury depends on first, the presence of trophic factor(s) which prevent death, induce growth and maintain the viability of the neurone and second, the regenerating neurites must overcome glial scars, extracellular matrices and white matter barriers to reinnervate their target. Attempts at promoting regeneration by using grafts of prosthetic material, Schwann cells and neural tissue have largely been unsuccessful. Although growth could be induced, penetration of regenerating neurites through damaged areas of the spinal cord has been limited. There is as yet very little beneficial functional recovery.


Effect of cholesterol and its autooxidation derivatives on endocytosis and dipeptidyl peptidases of aortic endothelial cells. The effects of cholesterol (CHO) and cholesterol autooxidation derivatives (CAD) on the endocytosis of cationized ferritin (CF) by endothelial cells have been investigated. The effect of both substances on the activity of lysosomal enzymes dipeptidyl peptidase I (DPP I) and dipeptidyl peptidase II (DPP II) was also studied. Treatment of rats with CAD induced striking alterations in the ultrastructure of endothelial cells and makes it impossible to analyze the effect of this toxin on endocytosis processes. In contrast, CHO-treated cells displayed a good ultrastructural preservation and showed an increased ability to endocyte ferritin, as compared with controls. Both DPP I and DPP II activities increased after 3 weeks of CAD or CHO treatment. Our results indicate that although CHO damage endothelial cells, the most important effects could be attributed to CAD which usually accompanies CHO-supplemented diets.


Early in-vitro histological chondral differentiation. In vitro chondrogenesis is possible in the chick embryo from stage 4 of Hamburger and Hamilton (1951), only 18-19 hours of incubation, before somite formation. In stage 4 of Hamburger and Hamilton (1951) the chondroblasts are placed laterally to the primitive streak and notochord cells are not necessary for cartilage differentiation.


Localization of blood coagulation factors in the germinal centers of human Peyer's patches. The immunohistochemical distribution of 15 blood coagulation factors in the germinal centers (GCs) of human Peyer's patches (PPs) was studied. Although factor VIII, active alpha-thrombin, and fibrinogen were hardly evident in the GCs, the majority of coagulation factors, such as kallikrein, high-molecular-weight kininogen, factors XII, X, IX, VII, V, XIIIa and XIIIb, prothrombin, anti-thrombin III and inactive alpha-thrombin were found, showing a lace-like staining pattern similar to that obtained with a monoclonal antibody, R4/23, specific for follicular dendritic cells (FDCs) in the GCs. By immunoelectron microscopy, positive reactions for factor X and XIIIa were found on the surfaces of FDCs, GC cells, and/or in the intercellular spaces of GCs, being especially marked on the surface of the labyrinth-like structure of FDCs. It is concluded that a majority of coagulation factors are localized in the GCs of human PPs. Furthermore, it is suggested that some of these coagulation factors have a close topographical relationship with FDCs.


Intimal thickening in arterial autografts. Role of the adventitial layer. In the present work, the repairing response of the iliac arterial wall is studied after carrying out autografts in segments of these vessels. The formation of the intimal hyperplasia, which occurred in all the cases, was followed at the biochemical level (tritium thymidine incorporation) and with light and electron microscopy. The adventitial layer showed great activity during the repairing process. We believe that it plays an important role not only in neoadventitial formation, but also in myointimal raising.


Differential proliferation of rat aortic and mesenteric smooth muscle cells in culture. Smooth muscle cells (SMC) from various arterial origins have been successfully maintained in culture. The present study evaluates the proliferative activity of aortic and mesenteric SMC in culture. Aortic and mesenteric SMC were obtained from male Wistar rats by explant and enzyme digestion techniques, respectively. Vascular SMC obtained by either method exhibited a characteristic hill-and-valley growth pattern in culture after confluence and were positively labelled with either anti-smooth muscle actin or myosin by an indirect immunofluorescent method. The rate of incorporation of thymidine into DNA and cell number counting were used as indices of proliferation in vitro. Vascular SMC from passages 4-33 were first synchronized with either Dullbecco's Modified Eagle's Medium (DME) or Ham's F-12 medium, supplemented with insulin-transferring-selenium (ITS), for 72 hours. SMC were then stimulated with 10% bovine serum for either 24 or 72 hours with the former processed for scintillation counting, the latter for cell number determination. The incorporation of tritiated thymidine into DNA following a 2 hour incubation was determined by scintillation counting after perchloric acid extraction. In terms of cell numbers, proliferative responses to bovine serum were determined by Coulter counting. Autoradiography was also carried out in some cultures to determine both thymidine and mitotic labelling indices. The rate of thymidine incorporation in aortic cells was 2-3 fold higher than in mesenteric cells. Aortic and mesenteric SMC lines exhibited similar cell cycle intervals in terms of total duration and individuals cycle parameters. However, the total thymidine index was higher in the aortic than mesenteric SMC.(ABSTRACT TRUNCATED AT 250 WORDS)


Sclerosing haemangioma of the lung.

Sclerosing haemangioma of the lung. The present paper describes a case of sclerosing haemangioma of the lung. Immunohistochemical analysis further supports its origin from respiratory epithelium, and confirms its minimal proliferative activity.


Neurotrophic factor-like effect of FPF1070 on septal cholinergic neurons after transections of fimbria-fornix in the rat brain. FPF1070 is an aqueous protein-free solution, which consists of 85% free amino acids and 15% small peptides. Our previous study showed a potent neurotrophic factor-like activity in cultured embryonic cells of dorsal root ganglia. The present study investigated whether FPF1070 regenerated the cholinergic cells in the medial septal nucleus after axonal transections by cutting the fimbria-fornix. Fimbrial transection reduced the number of septal cholinergic cells by 30 +/- 3.6%, compared with the number on contralateral sides at 4 weeks. Intraperitoneal injections of FPF1070 caused 49.9 +/- 6.3% of the cholinergic neurons to survive. Furthermore, the cell sizes of the cholinergic neurons were significantly different: 16.4 +/- 4.2 microns, 14.3 +/- 3.8 microns in FPF1070 treatment and vehicle treatment, respectively. These results indicated that FPF1070 prevents the degeneration and atrophy of impaired cholinergic neurons by systemic administration.


Effects of captopril on the development of rat doxorubicin nephropathy. The effects of a daily administration of an anti-converting enzyme inhibitor. Captopril (CPT) (100 mg/kg/orally), on the development of functional and morphological alterations induced in rats by a single injection (7.5 mg/kg/iv) of Doxorubicin (DXR) (Adriamycin*), were investigated. Twenty-four-hour protein excretion, urine output, food intake, water intake, and body weight gain were measured weekly for 30 days. Transmission and scanning electron microscopy observations were performed on kidney samples after 30 days. Four groups were studied. Group 1 were control rats. Group 2 were rats injected with DXR. Group 3 were rats injected with DXR and treated with CPT for 30 days. Group 4 were rats injected with DXR and treated with CPT for 15 days (CPT treatment started 15 days after DXR injection). Group 1 did not show significant functional or morphological changes. Group 2 showed severe proteinuria, significant increase in urinary volume within 2 weeks, significant body weight reduction and diffuse morphological changes. These changes mainly consisted of podocyte swelling, severe foot process fusion, and presence of casts within tubular lumen. Group 3, with respect to group 2, showed a significant reduction of the 24 h protein excretion and urine output. This group displayed morphological changes similar to those observed in group 2, but with a focal distribution. Group 4 showed functional and morphological changes comparable with those of group 2. It is concluded that CPT partially inhibits the development of the functional and morphological damage induced by DXR in the rat kidney. However, CPT did not influence the natural development of nephropathy when treatment started 15 days after DXR injection.


Etiology of the developing eye in myelencephalic blebs (my) mice. The etiology of the eye defects in myelencephalic blebs (my) mutant mice has been poorly understood for almost seventy years. Embryos from 9 to 14 1/2 days of gestation were subjected to Alcian blue 8GX staining for acidic glycosaminoglycan deposition in basement membrane structures of the developing eye in my stock and control specimens. In addition 12 day embryos were subjected to avidinbiotin-peroxidase labelling for laminin. At 9-9 1/2 days of gestation more Alcian blue positive extracellular matrix was found in the region between the optic vesicle and the overlying putative lens ectoderm in the my stock embryos. By 12 days, there was an irregular and lesser amount of deposition of glycosaminoglycans in the len's capsule and in the "inner limiting membrane" of the presumptive neural retina; however, the deposition of laminin appeared to be greater in the inner limiting membrane of the my eye. By 14 days, the damage to the eye in the my embryos can be quite extensive, and the deposition of glycosaminoglycans was very meager in this situation. It appears that irregular deposition of glycosaminoglycans in the extracellular matrix and possible increase in the amount of laminin in basement structures in my embryos indicate disruption of the normal histochemistry involved in the development of the eye. Altered histochemistry may in turn indicate changes in permeability between cells of the developing tissues which result in the blebbing.


Changes in the ventral dermis and development of iridophores in the anadromous sea lamprey, Petromyzon marinus, during metamorphosis: an ultrastructural study. The ultrastructural changes that take place in the ventral dermis along with the development of iridophores were examined in the anadromous sea lamprey, Petromyzon marinus, during metamorphosis. There is a disruption of all components of the ventral dermis and a reformation that results in a structure very similar to that prior to metamorphosis. Although not a dermal component, a layer of iridophores develops directly beneath the dermis during late metamorphosis. The dermal endothelium is lost by mid metamorphosis (stage 4) and the highly organized collagenous lamellae making up the bulk of the dermis become disrupted by the migration of fibroblasts into the region. Many of these fibroblasts are involved in the degradation of the lamellae. By stage 5 of metamorphosis some fibroblasts become highly active collagen synthesizing cuboidal shaped cells that align to form a layer above the reformed dermal endothelium. New lamellae are formed by these cuboidal cells which then divide and migrate into the lamellae where they assume the characteristic attenuated appearance of fibroblasts in the adult dermal lamellae region. Iridophores first appear during stage 5 directly beneath the dermal endothelium. Reflecting platelets develop from double membraned vesicles associated with the Golgi apparatus. By late metamorphosis, stacks of trapezoidal shaped platelets fill the cytoplasm of the iridophores. The significance of the changes in the dermis during metamorphosis are discussed. This work is part of a continuing series of studies on the connective tissues in the anadromous sea lamprey.


Peritoneal fine structure of inguinal hernia: a transmission electron microscope study. Fine structure of normal human parietal peritoneum served as control data for recording changes in the fine structure of the peritoneum of hernial sacs. In these sacs, mesothelial cells retracted, rounded up and some of them eventually separated altogether to give rise to wide open intercellular spaces thus creating unhindered passageways (stomata) between the subserosal connective tissue and the cavity of the sacs. There was a considerable collagen build-up in the subserosal fibrous tissue of hernial sacs. Occurrence of this fibrosis is at variance with an accepted surgical concept which suggests a defect in collagen synthesis as the cause of herniation. In some sacs mesothelial nodules and/or peritoneal adhesions were present. Certain cytological changes in the mesothelial cells of hernial sacs showed features in common with cells of malignant tumours in general, and features mimicking malignant mesotheliomas in particular. This is in spite of the fact that thorough gross and light microscopic examination of operative specimens and cytological evaluation of peritoneal effusion failed to reveal any evidence of malignancy. Pathologists should be aware of the consummate ability of mesothelial cells to mimic carcinomas in order to avoid possible diagnostic errors. In this report, an electron micrograph of peritoneal adhesion is being published for the first time in the literature. A syncytium-like firm bond between adjoining mesothelial cells constituted the adhesion which is obviously an irreversible process.


The ependymal surface of the fourth ventricle of the rat: a combined scanning and transmission electron microscopic study. The morphological features of the ependymal surface and supraependymal elements of the fourth ventricle of the rat were examined by scanning electron microscopy (SEM) and by the transmission electron microscopy (TEM). The results confirm the following aspects: 1) The presence of supraependymal elements and microvilli in the ependymal territories, including the sites where the cilia completely cover the ependymal surface; 2) The existence of cilia with oval or spherical thickenings together with supraependymal bulbs similar in size to those of the larger ciliary swellings; 3) Identification of the long supraependymal fibres with intermittent fusiform dilations observed under the SEM with the nerve fibres seen under the TEM; 4) The existence of intraventricular axodendritic synapses.


Morphology of epiphyseal apparatus of a ranid frog (Rana Esculenta). Morphological, histochemical and ultrastructural investigations on epiphyseal apparatus of Rana Esculenta were made. The most important findings were the following: 1) metaphyseal cartilage is localized inside proximal diaphyseal compact bone as a plug; 2) metaphyseal cartilage do not reduce in thickness during ageing; 3) metaphyseal cartilage do not show vascular invasion and do not mineralize in degenerative zone; 4) trabecular bone was not at all evident in this animal; 5) external periosteum is well vascularized and proliferates in correspondence to marginal epiphyseal end of the diaphyseal. From these results the hypothesis that the ranid frog bone growth is not due to metaphyseal metabolism (as in avian and mammals) but to bone periosteal marginal mineralization is reached.


Retinal epithelial fine structure in the southern fiddler ray (Trygonorhina fasciata). The morphology of the retinal epithelium (RPE), choriocapillaris and Bruch's membrane (complexus basalis) has been investigated by light and electron microscopy in an elasmobranch, the southern fiddler ray or guitarfish (Trygonorhina fasciata). The RPE consists of a single layer of cuboidal cells which display basal (scleral) infoldings as well as numerous apical (vitreal) finger-like processes which interdigitate with the photoreceptor outer segments. The lateral cell borders are relatively smooth and are joined in the mid-region by a series of tight junctions. Internally the RPE nucleus is large, vesicular and centrally located. Smooth endoplasmic reticulum (SER) is abundant while rough endoplasmic reticulum (RER) is scarce. Polysomes are however widespread and mitochondria are plentiful. Two unusual organelles are also noted. One consists of a membrane bound array of tubules while the other is a membrane bound structure consisting of a granular matrix with again an internal tubular array. This species possesses a choroidally located tapetum lucidum in the superior fundus and over this tapetal area, melanosomes are absent from the RPE cells. In non-tapetal locations a few melanosomes are present that do not appear to undergo photomechanical movements. Bruch's membrane is a pentalaminate structure with an almost continuous central elastic layer (lamina densa). The choriocapillaris forms a single layer of capillaries with a thin but only minimally fenestrated endothelium facing Bruch's membrane.


Photoreceptor fine structure in the southern fiddler ray (Trygonorhina fasciata). The fine structure of the retinal photoreceptors has been studied by light and electron microscopy in the southern fiddler ray or guitarfish (Trygonorhina fasciata). The duplex retina of this species contains only rods and single cones in a ratio of about 40:1. No multiple receptors (double cones), no repeating pattern or mosaic of photoreceptors and no retinomotor movements of these photoreceptors were noted. The rods are cylindrical cells with inner and outer segments of the same diameter. Cones are shorter, stouter cells with a conical outer segment and a wider inner segment. Rod outer segment discs display several irregular incisures to give a scalloped outline to the discs while cone outer segment discs have only a single incisure. In all photoreceptors a non-motile cilium joins the inner and outer segments. The inner segment is the synthetic centre of photoreceptors and in this compartment is located an accumulation of mitochondria (the ellipsoid), profiles of both rough and smooth endoplasmic reticulum, prominent Golgi zones and frequent autophagic vacuoles. The nuclei of rods and cones have much the same chromatin pattern but cone nuclei are invariably located against or particularly through the external limiting membrane (ELM). Numerous Landolt's clubs which are ciliated dendrites of bipolar cells as well as Müller cell processes project through the ELM, which is composed of a series of zonulae adherentes between these cells and the photoreceptors. The synaptic region of both rods (spherules) and cones (pedicles) display both invaginated (ribbon) synapses and superficial (conventional) synapses with cones showing more sites than the rods.


Ultrastructural localisation of acid phosphatase in intestinal eosinophilic granule cells (EGC) of rainbow trout (Oncorhynchus mykiss) following degranulation with capsaicin. Enzyme cytochemistry was used to investigate possible lysosome involvement in capsaicin induced degranulation of the eosinophilic granule cell (EGC) of the rainbow trout intestine. Three adult rainbow trout (Oncorhynchus mykiss) were injected intraperitoneally with capsaicin in a saline vehicle (0.5 micrograms.g-1 body weight). Following a 2 hour period of incubation, the fish were killed, and a mid portion of the intestine was dissected and fixed in cold glutaraldehyde buffered with sodium cacodylate. Vibratome sections were incubated in either reaction medium containing beta-glycerophosphate and cerium chloride in acetate buffer or substrate (beta-glycerophosphate) deficient control medium. Sections were then refixed in osmium tetroxide and processed for electron microscopy. Acid phosphatase was found to be localised within lysosomes. The enzyme was not found in the large cytoplasmic granules under normal or capsaicin-stimulated conditions. EGCs which had migrated to the lamina propria in response to the capsaicin stimulation had a distinct multivesicular granule morphology. These multivesicular granules did not contain acid phosphatase suggesting that this form of EGC degranulation is not a lysosomally mediated event.


Effects of light deprivation on prolactin cells in golden hamsters: an immunoelectron microscopic study. In the golden hamster light deprivation has been shown to induce gonadal regression and reduction of pituitary and plasma levels of prolactin (PRL). In the present study we examined changes in morphology and population ratios of three types of PRL cells 8 weeks after light deprivation, by means of blinding or exposure of hamsters to continuous darkness. In the pituitary of intact hamsters of either sex, which were entrained to a 14-h light: 10-h dark cycle, Type C cells with large secretory granules were the most numerous and Type A with smaller granules the least. After light deprivation the pituitary was found to contain remarkably atrophic PRL cells and showed a profound change in population ratio of PRL cell types, i.e., Type A cells prevailed over the other two types. Pituitary glands from light-deprived and concurrently pinealectomized hamsters exhibited structures and a population ratio of three types of PRL cells similar to those from intact animals. It is suggested that small-granule-containing PRL cells represent an inactive stage of PRL cells, whereas medium- and large-granule-containing cells are functionally active cells. The atrophy of PRL cells can account for the decreased pituitary level of PRL in light-deprived hamsters reported previously.


Percutaneous isolated liver perfusion for treatment of hepatic malignancy: preliminary report. Chemotherapy for primary or metastatic hepatic malignancy is limited by poor tumor response and dose-related systemic toxicity. As an alternative to chemotherapy infusion by vein or by the hepatic artery, the authors have developed a percutaneous technique of isolated liver perfusion that allows the regional delivery of high-dose chemotherapy to the liver with little systemic toxicity. After placement of a hepatic artery infusion catheter, an 18-F double-balloon catheter is placed into the inferior vena cava through the opposite femoral vein. Balloons are inflated above and below the hepatic veins, thus isolating hepatic venous outflow. The effluent passes through fenestrations in the catheter and is pumped through charcoal hemoperfusion filters where the drug is removed. The filtered blood is returned to the patient through the internal jugular vein. Fifteen treatments have been conducted in eight patients in a phase I dose-escalation study with use of 5-fluorouracil (5-FU). While it is premature to assess tumor response to isolated liver perfusion, the data demonstrate that the procedure is safe and is tolerated by patients. Pharmacokinetic studies show a 5-FU extraction of up to 85%, with minimal drug leakage into the systemic circulation. This technique shows potential for improving liver tumor response while decreasing systemic toxicity.


Initial experience with percutaneous placement of the PAS port implantable venous access device. The authors evaluated a new venous access port designed for peripheral venous insertion in the interventional radiology suite. Forty ports were placed in 40 patients in either the brachial, cephalic, or basilic vein under fluoroscopic guidance. These ports have been used for blood transfusion, blood sampling, parenteral nutrition, chemotherapy, and antibiotic therapy. The ports have been in use for 4,241 consecutive patients days. There have been no clinically apparent venous thrombotic complications and only one device-related infection. The cost and risk of complication are less than those for a surgically placed chest wall port, and the cosmetic result is excellent. This port has had excellent patient, nursing, and clinical acceptance.


Wallstent migration following deployment in right and left bile ducts. The Wallstent biliary endoprosthesis has recently been approved for treatment of malignant bile duct obstruction. Although minor changes in position have occurred, migration of these stents has been uncommon. The authors report a case in which migration occurred when stents were simultaneously deployed in the right and left bile ducts. Several mechanisms for this complication are postulated.


Low-dose urokinase regimen for the treatment of lower extremity arterial and graft occlusions: experience in 132 cases. In a retrospective review, a low-dose urokinase (UK) infusion regimen (mean, 87,000 U of UK per hour and 100 U of heparin per hour) was evaluated for lower extremity arterial and graft occlusions. Results of 132 infusions in 111 patients were analyzed to determine efficacy, limb salvage, and complications. Angiographic success was achieved with 126 infusions (95%), and amelioration of presenting signs and symptoms was achieved after 116 infusions (88%). Patients who underwent additional percutaneous procedures were more likely to have a successful outcome. There was no significant difference in success rates for patients receiving low-dose heparin through the arterial sheath (n = 101) versus those receiving concomitant systemic heparinization (n = 29), (P = .08) [corrected]. Of 88 threatened extremities (with rest pain, cold, ulcers, or gangrene), nine were amputated (limb salvage = 90%), accounting for 82% (nine of 11) of amputations in the overall study. Patients with zero- or one-vessel runoff before infusion were more likely to require limb amputation compared with the group with two- or three-vessel runoff before infusion (P less than .01). Major periprocedural complications occurred in nine of 132 (7%) infusions, five of which necessitated specific surgery and/or transfusion for bleeding. Pericatheter thrombosis was not encountered in either subgroup. This standard local low-dose infusion represents a safe and effective treatment for lower extremity arterial and graft occlusions.


Superior mesenteric artery embolism: treatment with intraarterial urokinase. Four patients with a superior mesenteric artery (SMA) embolism were successfully treated with intraarterial urokinase. Angiography showed partial SMA occlusion by intraluminal thrombus in two cases and almost total occlusion in two cases. Laparotomy was performed in the latter two cases, one of which required resection of infarcted bowel. Several additional reports of partially occluding SMA emboli treated successfully with streptokinase were found in the literature. The use of intraarterial thrombolytic drugs is an important addition to the treatment of mesenteric embolism that, in some cases, can eliminate or simplify surgical management.


Thromboembolectomy with the transluminal extraction catheter (TEC) as an adjunct to thrombolysis. Multiple surgical and percutaneous interventional radiologic techniques have been used to restore blood flow in an acutely ischemic extremity. The transluminal extraction catheter (TEC) system was used as a mechanical thromboembolectomy device to supplement pharmacologic thrombolysis in one patient. In this case, 40 hours of direct intraarterial infusion of urokinase into the occluded vascular segments of a threatened lower extremity resulted in incomplete thrombolysis. Therefore, a 7-F TEC system was advanced percutaneously through the occluded vessels with restoration of luminal patency in all vessels treated. No distal embolization occurred. The TEC system facilitated prompt recanalization of vessels occluded by acute thrombus superimposed on atherosclerotic disease.


Directional atherectomy treatment for hemodialysis access: early results. The Simpson atherectomy device was used to treat 12 intragraft stenoses, six complete subclavian vein occlusions, and 14 venous outflow stenoses in 24 patients undergoing hemodialysis. Patients were followed up clinically and by means of venography at approximately 1, 3, 6, 9, and 12 months after treatment. Twenty-eight atherectomy specimens were examined histologically. Twenty-six (81%) of 32 lesions were treated with initial technical success. Including technical failures, seven (58%) of 12 intragraft stenoses are angiographically patent at a mean of 5.0 months and five (50%) of 10 are clinically patent at 6 months. Three (50%) of six subclavian veins are angiographically patent at a mean of 5.6 months, and four (67%) of six are clinically patent at 6 months. Three (21%) of 14 venous outflow stenoses are angiographically patent at a mean of 5.0 months and five (38%) of 13 are clinically patent at 6 months. Histologic examination showed neointimal fibromuscular hyperplasia in 26 of 28 lesions. When 30% or less angiographic residual stenosis is used as the criterion for initial technical success, directional atherectomy appears to be effective therapy for intragraft stenoses and, with balloon angioplasty, for some catheter insertion-related subclavian occlusions. Directional atherectomy appears to have a recurrence rate for venous outflow stenoses similar to that for balloon angioplasty when the same criterion is used.


Transcatheter atrial septal defect occlusion devices: normal radiographic appearances and complications. Three transcatheter atrial septal defect (ASD) occlusion devices have been used in clinical trials during the past decade: the Rashkind ASD occluder, the Lock Clamshell occluder, and the buttoned double-disk device. The normal radiographic appearance of these three devices and radiographic findings in complications are presented. Of 12 transcatheter ASD occlusions performed, the buttoned double-disk device was used in eight patients, the Rashkind ASD occluder in three, and the Lock Clamshell occluder in one. Complications included both improper placement and partial dislodgment of the Rashkind ASD occluder device (n = 2), fracture of a metal arm of the Lock Clamshell device (n = 1), and detachment of the buttoned double-disk device with embolization into the right pulmonary artery (n = 1). Knowledge of the normal radiographic appearance of ASD occlusion devices and the findings in various complications will be necessary for radiologists as transcatheter ASD closure becomes more commonplace. Chest radiography is the primary method of detecting short- and long-term complications in patients following transcatheter ASD closure.


Vena caval occlusion after Simon nitinol filter placement: identification with MR imaging in patients with malignancy. The prevalence of inferior vena caval occlusion associated with the Simon nitinol filter (SNF) was studied at two institutions in the follow-up of filters placed over a 13-month period. Twenty-four consecutive patients with defined indications (contraindication to anticoagulation with pulmonary embolism or deep venous thrombosis [DVT], recurrent pulmonary embolism despite anticoagulation, or extensive DVT [eg, iliofemoral]) underwent placement of a SNF. This patient group includes a high proportion with pelvic or renal malignancy (54%, 13 of 24) or a history of other malignancy. Of these 24, physical examination at follow-up identified 10 symptomatic patients with unilateral or bilateral leg swelling. Of these 10, magnetic resonance imaging, with spin-echo and gradient-echo techniques, demonstrated IVC occlusion in five patients (50%). These data suggest that vena caval occlusion following SNF placement occurs more commonly than previously recognized. Possible contributing factors include reduced venous inflow in patients with prior nephrectomy or pelvic neoplasms, pelvic venous compression by tumor mass, and hypercoagulable states.


Traumatic lacerations of the aorta and great vessels with a normal mediastinum at radiography. The possibility of a "normal" mediastinum at conventional chest radiography in a patient with a lacerated aorta or great vessel from blunt thoracic trauma has not been evaluated objectively. All 1991 members of the Society of Thoracic Radiology were sent a questionnaire asking for examples of such cases. A similar questionnaire was placed in the newsletter of the Society of Cardiovascular and Interventional Radiology. The literature also was reviewed for cases. Seventy-eight of 327 questionnaires were returned with responses. Eight responders reported 12 examples of a normal mediastinum radiograph in a patient with a lacerated aorta. Review of the same radiographs by the authors yielded three normal and nine subtly abnormal mediastina. One additional normal radiograph was obtained of a patient with a lacerated great vessel. Another 16 cases of lacerated aortae (n = 12) and great vessels (n = 4) in patients with normal mediastina were found through a literature search; images from three of these were reviewed by the authors. Although this is an infrequent event, the mediastinum can be normal at plain chest radiography with traumatic lacerations of the aorta and great vessels.


Localization of the portal vein for transjugular catheterization: percutaneous placement of a metallic marker with real-time US guidance. Transjugular catheterization of the portal vein can be used to form a portosystemic shunt. Conventionally, the passage of a needle from the hepatic vein into the portal vein is performed with fluoroscopic monitoring only. Several methods to target the portal vein have been previously reported, including transhepatic venous catheterization, indirect portography (arterial catheterization), or skin marking based on ultrasound (US) mapping of portal landmarks. The authors used realtime US guidance to percutaneously place a small marking wire in the parenchyma next to the portal bifurcation. A 0.018-inch-diameter, 5-mm-long platinum wire is delivered through a 22-gauge echo-tipped needle placed adjacent to the right portal vein. This marking wire enabled rapid entry into the portal vein, helped avoid extrahepatic puncture, and was useful during stent deployment and positioning.


US-guided paraumbilical vein puncture: an adjunct to transjugular intrahepatic portosystemic shunt (TIPS) placement. Transjugular intrahepatic portosystemic stent-shunt placement has shown great promise as a means of protal decompression in patients with severe portal hypertension. Passage of a needle from the hepatic venous system into the portal venous system during this procedure may be technically difficult; while it would be advantageous to precisely target the portal vein, most methods of localization are themselves technically difficult, risky, or time-consuming. The authors describe a method of localization of the portal vein that, when feasible, appears to be both safe and technically simple. This method involves percutaneous catheterization of a paraumbilical portosystemic collateral vein under sonographic guidance.


Direct percutaneous ureteral approach for the treatment of ureteral stenosis or obstruction. Two cases are presented in which conventional approaches did not permit dilation of and stent placement in obstructed ureters. In patients with iatrogenic ureteral laceration or rigid ureteral kinking, direct percutaneous translumbar puncture may provide a safe alternative. The authors' technique is described.


Combined retrograde-antegrade ureteral stent passage: salvage procedure for a ureteral leak. The authors describe a stent placement procedure for treatment of an infected ureteral leak after failure of traditional antegrade and retrograde approaches. In this procedure, a guide wire was placed across the distal ureteral segment into a urinoma with use of cystoscopic guidance. Thereafter, an antegrade approach was used to pass a wire loop snare, capture the guide wire, and withdraw it through the proximal ureter for subsequent stent passage. This approach allowed percutaneous stabilization of a ureteral leak in a patient who would have otherwise required immediate surgical repair.


Comparison of filters in an oversized vena caval phantom: intracaval placement of a bird's nest filter versus biiliac placement of Greenfield, Vena Tech-LGM, and Simon nitinol filters. For patients with an oversized inferior vena cava (IVC) (diameter greater than 28 mm, corrected for magnification) who require vena caval filtration for prophylaxis against pulmonary emboli, the accepted treatment has been the biiliac venous placement of Greenfield filters. Because of its wide strut span, the Bird's Nest filter (BNF) has been successfully placed in patients having an oversized IVC. However, the effects of the BNF on caval blood flow and its clot-capturing ability in an oversized IVC are not clearly understood. The authors created a flow phantom simulating an oversized IVC with "iliac" tributaries of normal inner diameter to analyze flow turbulence, pressure gradients, and the clot-capturing ability of the BNF, tested within the "caval" segment of the phantom, and the Greenfield, Vena Tech-LGM, and Simon nitinol filters, tested in the "iliac" segments. All filters were tested for flow disturbances before and after clot capture. The authors' results demonstrate that within an oversized IVC, the BNF creates less flow disturbance and is less occlusive with clot capture than biiliac filters. The BNF displayed a clot-capturing ability equal to that of biiliac filters. Thus, for patients with an oversized IVC, these results suggest that placement of a single intracaval BNF is preferable to biiliac placement of filters.


In vitro comparison of the spiral Z stent and the Gianturco Z stent. A new spiral Z stent is described, and its characteristics are compared in vitro with those of the modified Gianturco Z stent. The spiral Z stent has a more uniform expansile force throughout its effective length; is more compressible, thus allowing for use of a smaller introductory catheter; and is more stable than the modified Z stent. Flexibility of both stent types is similar. Advantages of the spiral Z stent promise to be beneficial for clinical use.


Percutaneous nucleotomy with CT and fluoroscopic guidance. Automated percutaneous diskectomy was performed with use of computed tomographic (CT) and fluoroscopic monitoring. Degenerative disease of the intervertebral disk was treated with local administration of anesthesia and use of a nucleotome. One hundred ten patients with neurologic symptoms and morphologic changes of one segment were selected for treatment. Previous conservative therapy had been unsuccessful. Patients with completely prolapsed and sequestered fragments of herniated disks ("uncontained disk"), narrow intervertebral spaces, posterior osteophytes, diseased facet joints, and spinal stenoses were not considered candidates for percutaneous nucleotomy (PNT). After PNT, 82% of the patients had complete remission of their neurologic symptoms; Lasègue sign was negative or improved in 92%. In 18% (20 patients), the symptoms did not improve sufficiently; 11% (12 of 110) of these patients underwent surgical nucleotomy. There were no serious complications, in particular, no injuries to vital structures (nerves, thecal sac, arteries, veins), except for one case of spondylodiskitis. Guiding PNT with CT and fluoroscopy provides a safe procedure with good clinical results. The addition of CT has shortened the operation but increased over-all procedure time. In the future, a shift to outpatient treatment may offset the additional time and cost of including CT guidance.


Steel coil embolization supplementing filter placement in a patient with a duplicated inferior vena cava. Anatomic anomalies involving the inferior vena cava (IVC) can present both diagnostic and therapeutic challenges when percutaneous placement of a filter is considered. A patient with a duplicated IVC was treated with placement of a filter in the right-sided IVC and steel coil embolization of a smaller left-sided IVC.


Retrieval of intravascular foreign bodies with the snare and catheter capture technique. The authors report two cases of retrieval of iatrogenically placed intravascular metallic foreign bodies: a guide wire in the abdominal aorta and a guide-wire fragment in the inferior vena cava. The foreign bodies were retrieved with use of a new approach described as the "snare and catheter capture technique." This technique is useful with guide wires that are too stiff to safely remove doubled over.


Permanence and the dynamics of biological systems. A basic question in mathematical biology concerns the long-term survival of each component, which might typically be a population in an ecological context, of a system of interacting components. Many criteria have been used to define the notion of long-term survival. We consider here the subject of permanence, i.e., the study of the long-term survival of each species in a set of populations. These situations may often be modeled successfully by dynamical systems and have led to the development of some interesting mathematical techniques and results. Our intention here is to describe these and to consider their application to several of the most frequently used models occurring in mathematical biology. We particularly wish to include and cover those models leading to problems that are essentially infinite dimensional, for example reaction-diffusion equations, and to make the discussion accessible to a wide audience, we include a chapter outlining the fundamental theory of these.


A new method for regularization of the inverse problem of electrocardiography. The inverse problem of electrocardiography (specifically, that part concerned with the computation of the ventricular surface activation isochrones) is shown to be formally equivalent to the problem of identification and measurement of discontinuities in derivatives of body surface potentials. This is based on the demonstration that such measurements allow localization of the relative extrema of the ventricular surface activation map (given a forward problem solution), which in turn restricts the space of admissible solution maps to a compact set. Although the inverse problem and the problem of identifying derivative discontinuities are both ill-posed, it is possible that the latter may be more easily or justifiably resolved with available information, particularly as current methods for regularizing the inverse problem typically rely on a regularization parameter chosen in an a posteriori fashion. An example of the power of the approach is the demonstration that a recent Uniform Dipole Layer Hypothesis-based method for producing the ventricular surface activation map is largely independent on that hypothesis and capable in principle of generating maps that are very similar in a precise sense to those that would result from the usual epicardial potential formulation (assuming the latter were capable of producing intrinsic deflections in computed epicardial electrograms sufficiently steep to accurately compute the activation map). This is consistent with the preliminary success of the former method, despite the significant inaccuracy of its underlying assumption.


Properties of the solutions to certain equations arising in the central core model of the renal medulla. We discuss the mathematical properties of the solutions to two of the differential equations that arise in the central core model of the renal medulla. Explicit solutions are obtained for a particular functional form of the flux of solute.


Branching process with emigration--a genetic model. Solution of a genetic improvement problem under the model of assortative mating is proposed. This has been achieved through the technique applied to a branching process incorporating a generation-dependent emigration component. The model explains a population subject to culling against genes governing undesirable characters and this work has been tried for a diploid population with two alleles at a single locus, which may be extended to the multilocus case.


Hopf bifurcation in three-species food chain models with group defense. Three-species food-chain models, in which the prey population exhibits group defense, are considered. Using the carrying capacity of the environment as the bifurcation parameter, it is shown that the model without delay undergoes a sequence of Hopf bifurcations. In the model with delay it is shown that using a delay as a bifurcation parameter, a Hopf bifurcation can also occur in this case. These occurrences may be interpreted as showing that a region of local stability (survival) may exist even though the positive steady states are unstable. A computer code BIFDD is used to determine the stability of the bifurcation solutions of a delay model.


The effects of averaging on the basic reproduction ratio. This paper formalizes the process of averaging the mixing patterns of behaviorally distinct individuals or groups. This averaging process is shown to decrease or leave unaltered the basic reproduction ratio R0 in epidemiological models with symmetric transmission between groups.


Epidemic and demographic interaction in the spread of potentially fatal diseases in growing populations. The spread of a potentially fatal infectious disease is considered in a host population that would increase exponentially in the absence of the disease. Taking into account how the effective contact rate C(N) depends on the population size N, the model demonstrates that demographic and epidemiological conclusions depend crucially on the properties of the contact function C. Conditions are given for the following scenarios to occur: (i) the disease spreads at a lower rate than the populations grows and does not modify the population growth rate: (ii) the disease initially spreads at a faster rate than the population grows and lowers the population growth rate in the long run and the following three subscenarios are possible: (iia) the population still grows exponentially, but at a slower rate; (iib) population growth is limited, but the population size does not decay; (iic) population increase is converted into population decrease.


A mathematical model for the growth and classification of a solid tumor: a new approach via nonlinear elasticity theory using strain-energy functions. Medically, tumors are classified into two important classes--benign and malignant. Generally speaking, the two classes display different behaviour with regard to their rate and manner of growth and subsequent possible spread. In this paper, we formulate a new approach to tumor growth using results and techniques from nonlinear elasticity theory. A mathematical model is given for the growth of a solid tumor using membrane and thick-shell theory. A central feature of the model is the characterization of the material composition of the tumor through the use of a strain energy function, thus permitting a mathematical description of the degree of differentiation of the tumor explicitly in the model. Conditions are given in terms of the strain energy function for the processes of invasion and metastasis occurring in a tumor, being interpreted as the bifurcation modes of the spherical shell, which the tumor is essentially modeled as. Our results are compared with actual medical experimental results and with the general behavior shown by benign and malignant tumors. Finally, we use these results in conjunction with aspects of surface morphogenesis of tumors (in particular, the Gaussian and mean curvatures of the surface of a solid tumor) in an attempt to produce a mathematical formulation and description of the important medical processes of staging and grading cancers. We hope that this approach may form the basis of a practical application.


Predictions of antagonistic muscular activity using nonlinear optimization. Optimization theory is used more often than any other method to predict individual muscle forces in human movement. One of the limitations frequently associated with optimization algorithms based on efficiency criteria is that they are thought to not provide solutions containing antagonistic muscular forces; however, it is well known that such forces exist. Since analytical solutions of nonlinear optimization algorithms involving multi-degree-of-freedom models containing multijoint muscles are not available, antagonistic behavior in such models is not well understood. The purpose of this investigation was to study antagonistic behavior of muscles analytically, using a three-degree-of-freedom model containing six one-joint and four two-joint muscles. We found that there is a set of general solutions for a nonlinear optimal design based on a minimal cost stress function that requires antagonistic muscular force to reach the optimal solution. This result depends on a system description involving multijoint muscles and contradicts earlier claims made in the biomechanics, physiology, and motor learning literature that consider antagonistic muscular activities inefficient.


Interpreting consensus sequences based on plurality rule. Our goal is to help researchers interpret the results of a function, based on the concept of plurality rule, that calculates a consensus of a profile of molecular bases. By expressing the plurality rule function as a composition of simpler functions, we obtain both an algorithm to calculate the consensus result and an upper bound on the number of nonequivalent results. Consequently, when used to analyze molecular sequences such as DNA or RNA, the plurality rule function yields at most 48 nonequivalent consensus results. For problems of reasonable size, we describe an algorithm to calculate the probability that each consensus result would occur if the bases were equally likely to appear at every position of the plurality rule function's input profile.


A two-state recurrent stochastic model with time-dependent transition rates. The two-state recurrent stochastic model with time-independent transition rates is generalized to a model with time-dependent transition rates. The rates can be any general function of external time, that is, any general function of the calendar time in which the process unfolds. Formulas for the state transition probabilities, the proportion of individuals in a particular state at time t, the distribution function, and the expectation of the number of individuals in a particular state at time t are derived.


The attractiveness of the Droop equations. The Droop equations are a system of three coupled, nonlinear ordinary differential equations describing the growth of a microorganism in a chemostat. The growth rate of the organism is limited by the availability of a single nutrient. In contrast to the better known Monod equations, the nutrient is divided into external and internal cellular pools. Only the internal pool can catalyze growth. This paper proves that the Droop equations are globally stable. Based on a single combination of parameters, either the chemostat organism goes extinct or it tends to a fixed, positive concentration.


Efficient optimal decomposition of a sequence into disjoint regions, each matched to some template in an inventory. Given an amino acid sequence, we discuss how to find efficiently an optimal set of disjoint regions (substrings, domains, modules, etc.), each of which can be matched to some element of a predefined inventory containing, for example, consensus sequences, protosequences, or protein family profiles. A two-stage approach to sequence decomposition, consisting of the detection of all acceptable matches followed by the construction of an optimal subset of compatible matches, leads to computational difficulties. When the problem is reformulated in terms of network comparisons, it can be solved in time quadratic in the length of the sequence and linear with the number of templates in the inventory, by a single pass of a dynamic programming algorithm. This method has the advantage that the criterion for acceptable matches can be relaxed without materially affecting computing time. Except under special conditions it is more efficient than previous segmentation methods based on dynamic programming.


The growth of pure and simple microbial competitors in a moving distributed medium. The dynamics of pure and simple competition between two microbial species are examined for the case of interaction arising in a distributed and nonstagnant environment. The environment is modeled as a tubular reactor. It is shown that for relatively small values of the dispersion coefficient (i.e., for small, but nonzero, backmixing of the medium), the two competing populations can coexist in a stable steady state. It has been assumed that the species grow uninhibited and that if there are maintenance requirements they are satisfied from endogenous sources. From numerical studies it has been found that a necessary condition for coexistence is that the net specific growth rate curves of the two competitors cross each other at a positive value of the concentration of the rate-limiting substrate. The model equations have been numerically solved by using the methods of orthogonal and spline collocation.


A 10-year prognosis for childhood allergic rhinitis. The prognosis of allergic rhinitis was studied in 154 children aged 3-17 years at diagnosis by means of a detailed questionnaire administered 8-11 years later. The symptoms had completely disappeared in only 15 (10%) patients. The conjunctival symptoms, however, had disappeared or were controlled successfully by topical drug therapy in almost all, and 77 (50%) were managing without medication for allergic rhinitis. Twenty-five (23%) of the 110 children with seasonal allergic rhinitis had a perennial disease at follow-up, in contrast to seven (16%) of 44 with perennial allergic rhinitis originally who had only seasonal symptoms at follow-up. Asthma or wheezing had developed in 29 cases (19%) and was more common (p less than 0.01) among those with perennial allergic rhinitis (15 of 44) than among those with seasonal allergic rhinitis (14 of 110). No significant association was found between age at onset of symptoms, family history of atopic disease or type of treatment for allergic rhinitis and allergic rhinitis still present at follow-up or development of asthma during the observation period.


Regressed retinopathy of prematurity: the relationship between clinical risk factors of the newborn period and regressed retinopathy of prematurity severity in a preterm born population of Stockholm county 1976-81. In a retrospective study, clinical risk factors of the neonatal period were correlated with the severity of regressed retinopathy of prematurity (ROP) in a population of preterm infants (bw less than 1500 g and or gestational age less than 33 weeks). At the age of 5-11 years 134 out of 528 preterm born infants (25.4%) were found to be under ophthalmic care. Reliable information on eye fundus status could be obtained in 105 of them. Regressed ROP was found in 61, the moderate form in 48 (9.1%) and the severe form in 13 (2.5%) patients. Twelve patients (2.3%) had visual acuity of less than 0.3 on the worst eye and two (0.4%) of these patients were blind from ROP. Twenty-four clinical factors of the newborn period were correlated with the severity of regressed ROP. The results suggest that long oxygen exposure in combination with other factors interfering with retinal vasotonus are associated with the degree of the disease developed.


Re-evaluation of the whey protein/casein ratio of human milk. Total casein subunits as well as whey proteins were quantitated in human milk samples during lactation. Two independent methods were used: precipitation at pH 4.3 in the presence of Ca2+ followed by Kjeldahl analysis and polyacrylamide gradient gel electrophoresis (PAGGE) followed by densitometric scanning. Both methods yielded similar results: casein synthesis is low or absent in early lactation, then increases rapidly and subsequently decreases. The concentration of whey proteins decreases from early lactation and continues to fall. These changes result in a whey protein/casein ratio of about 90:10 in early lactation, 60:40 in mature milk and 50:50 in late lactation. These observations indicate that the synthesis and/or secretion of caseins and whey proteins is regulated by different mechanisms. In addition, the relative proportion of the different beta- and kappa-casein subunits was found to vary throughout lactation.


Immunoglobulin G subclasses in human colostrum, milk and saliva. Previous studies have suggested local production of IgG4 in human colostrum and mature milk. We extended these observations to examine all IgG subclasses in mammary secretions and in saliva, a mucosal secretion. In human colostrum and milk, the geometric mean percentages of IgG contributed by IgG2 were 44% and 43%, respectively, and by IgG4, 6% in both. These percentages are significantly increased compared to the contributions in matched plasma, 29% for IgG2 and 2% for IgG4. The contribution of IgG1 (47%) and IgG3 (less than 4%) were decreased compared to plasma which contained 64% IgG1 and 6% IgG3. Similarly, in salivary secretions the percentages of IgG contributed by IgG2 and IgG4 were increased compared to serum while the percentage of IgG1 was decreased. IgG3 was not measurable in any saliva specimen by the technique used. These data demonstrate that IgG subclass distribution in two separate mucosal secretions is uniquely different from that in matching plasma or serum.


Supplementation of an adapted formula with bovine lactoferrin: 1. Effect on the infant faecal flora. The development of the infant faecal flora was studied over the first three months of life in infants receiving breast milk, a modern adapted formula and adaptations of this formula. Breast-fed infants developed a flora rich in Bifidobacterium sp. Facultative anaerobes were ubiquitous, but in relatively small numbers within the diet group. Other obligate anaerobes, such as Clostridium sp. and Bacteriodes sp. were rarely isolated. Standard formula produced a flora rich in bifidobacteria, but the growth of facultative organisms was not suppressed by this diet. Clostridium sp. and Bacteroides sp. were more common in this feeding group. After the addition of lactoferrin at 10 mg/100 ml to the formula diet, a flora similar to that of the standard formula-fed babies was achieved. Lactoferrin at 100 mg/100 ml was able to establish a "bifidus flora" in half of the babies given this formula, but only at age three months. Clostridium sp. and Bacteroides sp. were common faecal isolates from babies receiving both the lactoferrin diets.


Blood T and B lymphocyte subpopulations in healthy infants and children. Monoclonal antibodies and flow cytometry are now used routinely in the diagnosis of many malignant diseases and primary and secondary immunodeficiency states. Technical advances have improved the identification of blood lymphocyte subsets and reliable normal values are now obtainable. Such values have been reported for adults but not for children. We report both absolute and percentage normal values for lymphocytes and their subsets in infants and children of different ages. Our findings show that the absolute and percentage values for most lymphocyte markers differ substantially not only between children and adults, but also between children from different age groups. In infants, erythroid cell contamination of Ficoll gradient-density isolated mononuclear cells must be removed to obtain reliable flow cytometry values.


Gastroesophageal reflux in children with recurrent abdominal pain. In this study we investigated the presence of gastroesophageal reflux in children with recurrent abdominal pain and its possible relationship to food intolerance-associated duodenal inflammation. Twenty-four-hour intra-esophageal pH monitoring, an endoscopic duodenal biopsy and a small bowel 51Cr-EDTA permeability test were performed in 25 children with recurrent abdominal pain. In 14 cases (56%) the pH monitoring was abnormal, pointing to the presence of pathological gastroesophageal reflux. Treatment of gastroesophageal reflux in the latter patients resulted in resolution or improvement of abdominal pain in 10 cases (71%). Gastroesophageal reflux did not appear to be associated with either intestinal permeability to 51Cr-EDTA or duodenal biopsy findings. We conclude that pathological gastroesophageal reflex is a frequent finding in children with recurrent abdominal pain, that it is unrelated to duodenal inflammation and that there might be a causal relationship between pathological gastroesophageal reflux and recurrent abdominal pain in children.