Neurotensin-like Peptides in the CNS of Lampreys: Chromatographic Characterization and Immunohistochemical Localization with Reference to Aminergic Markers

Neurotensin (NT)-like peptides in the CNS of the lamprey Lampetra fluviatilis were studied by radioimmunoassay (C-terminal specific NT antiserum), reverse-phase HPLC and immunohistochemistry. Multiple peaks of NT-immunoreactive (-ir) material were observed upon HPLC, of which a major peak eluted in the position of bovine NT. Immunofluorescence histochemistry showed that a monoclonal antibody recognizing the N-terminal (1 - 11) fragment of NT, as well as two polyclonal NT antisera labelled a large number of cell bodies in the periventricular area of hypothalamus, including the postinfundibular commissural nucleus and the ventral and dorsal hypothalamic nuclei. Additional groups of NT-ir cells were observed in the preoptic nucleus, the postoptic commissural nucleus, the mesencephalic tegmentum (L.fluviatilis), and in the spinal cord (L.fluviatilis and Ichtyomyzon unicuspis). Dense NT-ir fibre plexuses were present in the caudal hypothalamus, corpus striatum, ventral mesencephalon, and in the dorsal horn and lateral margin of the spinal cord. At the ultrastructural level the lateral spinal margin showed NT-ir terminal structures, which in most cases were not associated with synaptic specializations, although occasional synaptic contacts with unlabelled elements were found. The relation between NT-ir and monoamine-containing cells was examined with immunofluorescence double-staining, using antisera to tyrosine hydroxylase (TH), 5-hydroxytryptamine (5-HT), and histamine respectively. In the periventricular nuclei of hypothalamus numerous TH-, 5-HT-, as well as histamine-ir cells were located in close association with NT-ir cells, but none of the aminergic markers could be detected within NT-ir neurons. The chemical properties as well as the anatomical distribution of lamprey NT-like peptides show several similarities with those present in mammals, suggesting that NT-containing neuronal systems in the CNS developed early in vertebrate phylogeny.     

Cancer patients who refuse treatment

The value of cancer treatment was assessed using a natural experiment where patients who refused treatment served as no-treatment controls in a situation where withholding treatment to form a control group is unethical. Each cancer patient who refused treatment in Alberta, Canada between 1975 and 1988 was compared with five subjects who accepted treatment, matched on cancer site, age, number of cancers, and time period. Variables associated with treatment-refusal were included in Cox's proportional hazards model of survival, with death from cancer as the endpoint and deaths from other causes as censored observations. Treatment was refused at a rate of 7.5 per 1,000. One-third of patients who refused treatment had lung cancer and most had unstaged disease. Treatment refusal was associated with a difference in median survival of approximately nine months. Site-specific analyses showed a range of effects. Case fatality among the treated patients fell by approximately 10 percent during the 14-year study period. Even in advanced disease, treatment can result in improved survival. However, the results of this study must be interpreted with caution and cannot be generalized to all cancer patients.Dr Huchcroft and Mr Snodgrass are with the Alberta Cancer Board, Calgary, Alberta, Canada. Address correspondence to Dr Shirley Huchcroft, Senior Scientist, Division of Epidemiology and Preventive Oncology, Alberta Cancer Board, Calgary, Alberta, Canada T2N 4N2.     

MIR204 n.37C>T variant as a cause of chorioretinal dystrophy variably associated with iris coloboma,early-onset cataracts and congenital glaucoma

Four members of a three-generation Czech family with early-onset chorioretinal dystrophy were shown to be heterozygous carriers of the n.37C>T in MIR204. The identification of this previously reported pathogenic variant confirms the existence of a distinct clinical entity caused by a sequence change in MIR204. Chorioretinal dystrophy was variably associated with iris coloboma, congenital glaucoma, and premature cataracts extending the phenotypic range of the condition. In silico analysis of the n.37C>T variant revealed 713 novel targets. Additionally, four family members were shown to be affected by albinism resulting from biallelic pathogenic OCA2 variants. Haplotype analysis excluded relatedness with the original family reported to harbour the n.37C>T variant in MIR204. Identification of a second independent family confirms the existence of a distinct MIR204-associated clinical entity and suggests that the phenotype may also involve congenital glaucoma.     

Partial Artificial Heart (ALVAD) Use with Subsequent Cardiac and Renal Allografting in a Patient with Stone Heart Syndrome

The abdominal left ventricular assist device (ALVAD) is an order of magnitude more effective than conventional intra-aortic balloon pumping (IABP) in unloading and providing circulatory support to the failing left ventricle. This is a report of a unique case which demonstrates that in the absence of pulmonary vascular obstruction or constriction, the ALVAD can substitute for both left and right heart function. A 21-year-old patient with a congenital bicuspid aortic valve developed acute valvular endocarditis which rapidly progressed to congestive heart failure. An operation was undertaken, the mitral and aortic valves were excised and replaced by porcine heterografts, and a fistula from the right sinus of Valsalva to the right ventricle was closed. When coronary circulation was restored, irreversible ischemic contracture of the left ventricle, or "stone heart" syndrome, developed and emergency ALVAD or partial artificial heart implantation was effected. This device functioned as a total artificial heart for nearly six days, while a donor heart was sought. The patient then underwent removal of the ALVAD and cardiac and renal allografting. The transplanted heart functioned well, but the patient expired fifteen days later from gram-negative sepsis.     

Isoprenaline increases brain concentrations of administered l-dopa and l-tryptophan in the rat

A small dose of isoprenaline or saline was administered intraperitoneally to rats 20 min before the administration of one of the amino acids l-dopa or l-tryptophan. Isoprenaline caused a marked increase in the brain concentration of the administered amino acid. Isoprenaline has previously been shown to cause a decrease in at least some of those plasma amino acids which compete with l-dopa and tryptophan for carrier-mediated transport into the brain. The effect of isoprenaline on the concentrations of dopa and tryptophan in the brain is suggested to be at least partly caused by a change in the relationship between endogeneous and administered amino acids. It is also possible that a direct effect of isoprenaline on the blood-brain barrier transport system contributes to the effect.The reported finding might be of clinical interest in view of the therapeutic importance of aromatic amino acids with a central site of action.     

Synchronous primary carcinomas of the ampulla of vater and ascending colon in a patient with multiple flat adenomas

Multiple primary cancers occurring in the same patients have been reported to represent 1.8–3.9% of all cancers. The majority of all patients reported to have had a combination of simultaneous neoplastic changes in the ampulla of Vater and the colon showed familial adenomatous polyposis (FAP) syndrome. Variants of familial adenomatous polyposis coli are: attenuated adenomatous polyposis coli (AAPC, previously also known as flat adenoma syndrome) and multiple adenoma coli. AAPC is characterized clinically by many, but usually fewer than 100, colonic lesions that are characteristically slightly elevated and plaque-like, with a reddish surface and sometimes central depression. Genetically it represents an extremely rare variant of FAP. Another group of individuals, so-called multiple adenoma patients, have a phenotype similar to AAPC, but most have no demonstrable germ-line adenomatous polyposis coli mutation, as do patients with FAP or AAPC. However, there have been only a few reports that discussed concurrent neoplastic changes in the ampulla of Vater and colon in patients with multiple colonic flat adenomas, but without the florid phenotype of classical FAP. We present rare clinical course of a patient with multiple (more than 60) flat adenomas in the proximal colon and two primary cancers: of the ampulla of Vater and of the ascending colon. This patient and his family history did not show polyposis compatible with FAP or hereditary nonpolyposis colorectal cancer (HNPCC) syndrome.     

Effect of Systemic Pretreatment With Betamethasone on the Bacterial Flora,Inflammatory Response,and Polyp Formation in Experimentally Infected Rabbit Maxillary Sinus Mucosa

To investigate possible effects of corticosteroids on polyp formation and local bacterial colonization, pneumococcal sinusitis was experimentally induced in rabbits pretreated with betamethasone or saline. After 7 days, macroscopic polyps were counted post-mortem and on histologic slides after serial sectioning. Histologic sections were also examined with light microscopy. Macroscopic polyps were significantly fewer in animals given betamethasone, while there was no difference regarding the number of microscopic polyps. Ingrowth of pathogenic microorganisms was found in five of eight rabbits given placebo but in none of the animals treated with corticosteroids (P < 0.05). The reduced number of pathogenic strains in these animals may be explained by a better-preserved local host defense. The lower number of macroscopic polyps in the same animals could be because of a delayed mucosal repair and subsequent polyp formation.