Tumor hypoglycemia: deficient splanchnic glucose output and deficient glucagon secretion.

Fasting hypoglycemia occurred in a patient with a histologically benign mesothelioma; the serum insulin was low (2-4 muU./ml.), as was the glucose utilization rate. Splanchnic glucose output was markedly decreased on direct measurement (21 mg./min.; normal: 108-180 mg./min.). Splanchnic uptake of gluconeogenic substrates plasma glucagon was low normal during hypoglycemia and responded poorly to oral and intravenous alanine. The nonsuppressible insulin-like (NSILA-s) and somatomedin-like activities of the serum were not elevated, and the tumor did not release insulin-like activity on incubation nor did it contain somatostatin. The marked decrease in splanchnic glucose output was the principal cause of hypoglycemia, was associated with an apparent decrease in glycogenolysis, and was at least partly due to deficient glucagon secretion. The relationship of the tumor to these defects is unclear. The tumor may have secreted an unknown insulin-like material affecting primarily the liver and/or pancreatic alpha cell. The approach used here may serve as a paradigm for the analysis of hypoglycemia not caused by excessive insulin.

Paralytic shellfish poison (saxitoxin family) bioassays: automated endpoint determination and standardization of the in vitro tissue culture bioassay, and comparison with the standard mouse bioassay.

Mouse neuroblastoma cells swell and eventually lyse upon exposure to veratridine, which, when added together with ouabain, enhances sodium ion influx. In the presence of saxitoxin (STX), which blocks sodium channels, the action of the other two compounds is inhibited and the cells remain morphologically normal. A tissue culture bioassay using mouse neuroblastoma cells, developed by Kogure and colleagues, takes advantage of these principles; in this bioassay, the fraction of the cells protected from the actions of ouabain and veratridine is in direct proportion to the concentration of STX and its analogues. We have modified this bioassay, improving its convenience and speed by eliminating the need to count individual cells to determine the saxitoxin equivalents, and instead have employed a microplate reader for automated determinations of absorbances of crystal violet from stained neuroblastoma cells. When these changes and other minor technical modifications were tested in the tissue culture bioassay systematically, we found the lower detection limit to be around 10 ng STX equivalents (eq) per ml of extract ( = 2.0 micrograms STX eq/100 g shellfish tissue). Our version of the tissue culture bioassay was compared with the standard mouse bioassay using 10 acid extracts of dinoflagellates (Alexandrium excavata and A. fundyense) and 47 AOAC extracts of shellfish tissues. The tissue culture bioassay provided results virtually identical to those obtained with the mouse bioassay (r > 0.96), and moreover, was considerably more sensitive. The results gained from high performance liquid chromatographic (HPLC) analysis of 12 of the same extracts were less consistent when compared with the results from both bioassay methods. The automated tissue culture (neuroblastoma cell) bioassay may be a valid alternative to live animal testing for paralytic shellfish poisoning.

Induced resistance to infection of lobsters Homarus americanus by Aerococcus viridans (var.) homari, the bacterium causing gaffkemia.

A vaccine composed of steam sterilized (autoclaved) cells of a virulent strain of Aerococcus viridans (var.) homari was effective in protecting lobsters Homarus americanus against gaffkemia. At 15 degrees C the heat-killed vaccines (HKV) at concentrations between 1 and 5 x 10(7) particles kg(-1) lobster body wt induced maximal protection in induction periods ranging from 7 to 11 d. Protection was substantial over the course of a 30 d post-induction trial period. Spring-caught lobsters (i.e. those more fully rehabilitated following ecdysis) gained more protection (LD50 = 1.9 x 10(4)) from the vaccination than did those caught in the late fall-early winter period (lobsters that were not yet fully recovered from ecdysis) (LD50 = 3.2 x 10(3)). The protection offered by the HK vaccine was comparable to that induced by a vaccine produced by incubating the pathogen with low concentrations (2 pg ml(-1)) of the antibiotic vancomycin. The bacterins produced by both methods exhibited similar new properties: (1) agglutination at low titres by lobster hemolymph serum, suggesting an impaired capsule layer, and (2) increased permeability to the large Alcian Blue molecule. With both vaccines, the protection may be a direct result of increased exposure to intact bacterial cell structures by the lobster defences, an exposure which otherwise would be prevented by an intact capsule.

Disability 1986 and beyond: 11 years on.

Rehabilitation medicine is the fastest growing specialty in the UK. It is timely to take stock of the present structure and assess what needs to be done to ensure its appropriate development in the future.

The Silver-Russel syndrome: a case with sexual ambiguity, and a review of literature.

A 38-month-old patient with Silver-Russel syndrome (SRS) and ambiguous genitalia had a 46,XY karyotype on leukocyte and fibroblast cultures. This is the third SRS child with ambiguous genitalia described in the literature. In a review of the findings in 148 reported cases of the syndrome, abnormalities occurring in over 50% of the cases are short stature, craniofacial dysproportion, low birth weight, term gestation, body asymmetry, incurved fifth digits, normal intelligence, short fifth digits, and down-curved corners of the mouth (shark mouth).

Vitamin D deficiency rickets. Two cases with faulty infant feeding practices.

Two cases of vitamin D deficiency rickets verify the occurrence of deficiency rickets in the United States in 1973. The two cases demonstrate the need for periodic reviews of feeding practices, especically when the possibility of so-called milk allergy is postulated. This may lead to avoidance of milk products. Fortification of various kinds of food with vitamin D does not ensure the protection from nutritional rickets of all children with peculiar feeding habits.

Microbial utilization of the neurotoxin domoic acid: blue mussels (Mytilus edulis) and soft shell clams (Mya arenaria) as sources of the microorganisms.

The neurotoxin domoic acid is produced in quantity by the diatom Pseudo-nitzschia multiseries and is released to the environment directly and indirectly via food chains. Presumably there is a mechanism for the biodegradation and disposal of domoic acid and as bacteria are logical candidates for such an activity, a search for bacteria competent to carry out biodegradation of domoic acid was initiated. Extensive trials with a wide variety of bacteria isolated mainly from muds and waters taken from the marine environment showed that the ability to grow on or degrade domoic acid was rare; in fact, domoic acid was inhibitory to resting cells or growing cultures of most of these bacteria. In contrast, using enrichment techniques, it was possible to isolate from molluscan species that eliminate domoic acid readily, i.e., blue mussels (Mytilus edulis) and soft-shell clams (Mya arenaria), bacteria that exhibited growth with and biodegradation of domoic acid when supplemented with low concentrations of growth factors. The species that retain domoic acid for lengthy periods, such as sea scallops (Placopecten magellanicus) and red mussels (Modiolus modiolus), only occasionally yielded bacteria with this capability. The differences may be a result of the mechanisms used by the different shellfish in dealing with domoic acid, i.e., freely available in the blue mussels and soft-shell clams but likely sequestered in the digestive glands of sea scallops and red mussels and thus, largely unavailable for bacterial utilization. The results show that Mytilus edulis and Mya arenaria, almost uniquely, are prime and reliable sources of domoic acid utilizing bacteria. These findings suggest a strong possibility that autochthonous bacteria may be significant factors in the elimination of the neurotoxin in these two species of shellfish.