Induction of islet cytodifferentiation by fetal mesenchyme in adult pancreatic ductal epithelium.

Recombinant tissue consisting of adult ductal epithelium isolated from pancreas and fetal mesenchyme was transplanted subcutaneously in the inguinal region of nude mice or epididymal fat pads of rats with a tissue chamber device for short-term (8-day) or long-term (6- to 12-wk) duration. We found that recombinant tissue underwent morphogenesis and cytodifferentiation, thereby forming islets that contained cells immunocytochemically positive for insulin and glucagon. Islet cytodifferentiation occurred in approximately 20% of the recombinants. In recombinants that developed into islets, the tissue was always in close association with an extracellular matrix, nerves, and blood vessels. Controls consisting of mesenchyme alone or duct epithelium alone showed no evidence of morphogenesis of cytodifferentiation. Pancreatic rudiments were also implanted to serve as positive controls. This is the first demonstration of islet cytodifferentiation from adult duct epithelium.     

Prospective study of bacterial and viral contamination of exercise equipment.

OBJECTIVE: Transmission of bacterial and viral pathogens is known to occur by hand contact with fomites. Exercise equipment in public facilities may serve as such fomites. It is not known whether equipment disinfection might reduce microorganism colonization. We performed studies to address these issues. DESIGN: Observational study of bacterial and viral culture results from hand-contact surfaces of exercise equipment, pre-exercise and postexercise; prospective study of viral culture results before and after intervention with disinfection solution. SETTING: Two fitness centers in a military community. INTERVENTION: One week trial of twice-a-day equipment disinfection. MAIN OUTCOME MEASURES: Type and number of bacteria and type of viruses present on equipment before and after exercise; prevalence of viral culture positivity on equipment before and after intervention. RESULTS: Bacterial cultures of body contact surfaces on equipment revealed benign bacterial species (coagulase-negative staphylococci, diphtheroids, and so forth) but no pathogenic bacteria whether obtained pre-exercise or postexercise, or whether from aerobic versus weight training equipment. Viral cultures revealed the presence of viruses (generally rhinoviruses) on 63 of 100 (63%) hand-contact surfaces of equipment. Weight equipment was significantly more often contaminated than aerobic equipment (73% vs. 51%; P = 0.026). Disinfection of equipment did not lower the prevalence of virus isolation (48% positive before cleaning; 86% positive after cleaning). CONCLUSIONS: There is little risk of exposure to pathogenic bacteria on exercise equipment. Such equipment may commonly serve as fomites for the transmission of viruses. These data do not suggest that disinfection of exercise equipment will offer significant protective effects against virus exposure.     

Influence of rigid contact lens base curve radius on tear pump efficiency.

The effects of rigid contact lens base curve radius changes on tear pump efficiency were determined by measuring oxygen uptake on six with-the-rule corneas (with toricities between 0.37 and 1.00 D) under three conditions: (1) normal open eye, (2) after 5 min of static (without blinking) wear of polymethyl methacrylate (non-gas permeable) contact lenses, and (3) after 5 min of dynamic (with blinking once every 5 s) wear of the same lenses. The difference between the oxygen uptake rates measured under static and dynamic conditions provides an index of tear pump efficiency. Each subject wore a series of five lenses: fitted on K and 0.05 or 0.10 mm steeper and flatter than the flattest corneal meridian. The overall diameter of all lenses was 8.8 mm, the optic zone was 7.4 mm, the axial edge lift was 0.09 mm, and all other parameters were constant. The contact lens fitted on K was associated with the greatest central corneal oxygen debt under static conditions, whereas the same lens also provided for the best tear exchange with the blink. In addition, better tear exchange was found to be associated with larger palpebral aperture sizes.     

Two-tone suppression, excitation and the after effect in rate responses in auditory nerve fibres in the cat.

Responses were recorded from single, auditory nerve fibres in the anaesthetized cat. Acoustic stimuli consisted of two tones, one of which was at characteristic frequency (CF), the other (the suppressor) was at considerably lower frequency. Tones were presented in simultaneous and sequential configurations. For simultaneous presentations, well-known response properties were observed. The rising limb of the two-tone rate-intensity function closely matched that of the appropriately adapted response to the suppressor tone presented alone. Also, whether strongly suppressed relative to CF-driven rate, or equal to CF-driven rate, rate responses to the two-tone stimuli persisted unchanged when the CF tone was terminated and the suppressor tone continued alone. These results support the hypothesis that the suppressor tone has dual influences, suppressive and excitatory, that are distinct and additive. Peristimulus response histograms confirm in the cat that depression and slow recovery of sensitivity to CF may follow termination of the suppressor tone, as reported for the guinea pig [Hill, K.G. and Palmer, A.R. (1991) Hear. Res. 55, 167-176]. This delay in recovery of normal sensitivity to CF appeared to be directly related to the amount of excitation of the fibre that is attributable to the suppressor tone. A similar, delayed re-establishment of sensitivity also occurred in the response to a tone at CF, presented immediately following excitation by a suppressor tone. However, no delay occurred in the onset of response to the suppressor when preceded by the CF tone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pathophysiology of experimental leishmaniasis: the role of parasite physiology in the development of metastatic disease

This paper addresses the issue of how physiological properties of Leishmania determine the pattern of development of disseminated leishmaniasis in the mammalian host. It presents direct experimental evidence from in vivo studies that species of Leishmania differ in their capacity to multiply in cutaneous and visceral sites which results in differences in the pattern and rate of development of leishmaniasis. It was found that Leishmania mexicana amazonensis begins to multiply in the cutaneous site of inoculation within 7 days. Parasites, detected in the liver and spleen at 4 weeks, increased 100-fold during the next 4 months. However, the slow multiplication of L. mexicana amazonensis in the liver and spleen was more apparent than real. Parasites implanted in those organs of athymic nude mice by an intravenous injection were rapidly eliminated with a half-time of 16 hr. Thus, the parasites found in small numbers in the liver during the development of disseminated cutaneous disease in mice are most likely those which have been recently removed from the blood. Those few parasites that are not removed from the blood can establish metastatic foci in distant cutaneous sites, and replicate progressively once there.     

A monoclonal antibody to a parasympathetic neurotrophic factor causes immunoparasympathectomy in mice

A monoclonal antibody capable of blocking the biological activity of the ciliary neurotrophic factor purified from bovine cardiac muscle has been produced. This antibody, when administered perinatally to mice, causes a failure of the normal development of the parasympathetic innervation of the iris as determined by assay for the activity of the cholinergic marker enzyme choline acetyltransferase. The same treatment has no effect on the adrenergic neuronal marker, tyrosine hydroxylase. This immunoparasympathectomy suggests that the ciliary neurotrophic factor has an essential role in regulating the development of the mammalian parasympathetic nervous system.     

Long-term risk of second malignant neoplasm after a cancer in childhood

The risk of subsequent second malignant neoplasm was studied in a cohort of 634 patients, treated for a childhood cancer at the Gustave Roussy Institute between 1942 and 1969, and in complete remission five years after diagnosis. The most frequent types of first primary cancers (FPC) were Wilms' tumours (28% of the children), neuroblastomas (16%), lymphomas (12%) and soft tissue sarcomas (11%). Median follow-up duration after FPC was 19 years. Thirty-two patients (obs = 32) developed a total of 35 second cancers. Bone, thyroid, connective tissues and skin were the most frequent types of second cancer, with six patients for each type. The average annual incidence of second cancer was 0.36%. The average annual incidence for the periods 5-9, 10-14, 15-19, 20-24 and 25+ years after FPC was respectively 0.16%, 0.34%, 0.36%, 0.71% and 1.18%. The cumulative incidence of second cancer for the periods 5-20, 5-25 and 5-30 years after FPC was, respectively, 4.3% (95% CI: 2.8-6.6%), 7.8% (95% CI: 5.1-11.8%) and 13.0% (95% CI: 8.2-20.0%). The expected number of cancers in the cohort, computed from Danish cancer incidence data, was exp = 2.2. When compared to this expected number, the average annual excess incidence of second cancer, defined as obs-exp divided by the number of person years of observation, was 0.33%. This rose from 0.15% for the period 5-9 years after FPC to 1.09% for the period beginning 25 years after FPC. The standardised incidence ratio of second cancer (i.e. obs/exp) was 15 (95% CI: 10-21), and was fairly constant in the period extending from 15 to 20 years after FPC diagnosis. Obs/exp was equal to 25 for the patients who had had chemotherapy and equal to 9 for those who had not. Cyclophosphamide seemed less carcinogenic than the other alkylating agents. Obs/exp was similar for the patients who had received radiotherapy and for those who had not. The risk of cancer increased with age in the reference population and increased faster in the cohort, because the standardised incidence ratio is constant over a long period.     

Postamputation Pain and Sensory Changes in Treatment-naive Patients: Characteristics and Responses to Treatment with Tramadol, Amitriptyline, and Placebo

Background: Pain after amputation is common but difficult to treat, and few controlled treatment studies exist.

Methods: In the current study, 94 treatment-naive posttraumatic limb amputees with phantom pain (intensity: mean visual analog scale score [0-100], 40 [95% confidence interval, 38-41]) were randomly assigned to receive individually titrated doses of tramadol, placebo (double-blind comparison), or amitriptyline (open comparison) for 1 month. Nonresponders were crossed over to the alternative active treatment.

Results: After 1 month, phantom pain intensity was 1 (0-2) in the 48 tramadol responders (mean dose, 448 mg [95% confidence interval, 391-505 mg]), 0 (0-0) in the 40 amitriptyline responders (55 [50-59] mg), and 0 (0-0) in the 2 placebo responders, with similar effects on stump pain. Cytochrome P-450 2D6 slow metabolizers derived greater analgesia from tramadol and less from amitriptyline compared with fast metabolizers in the first treatment week (P < 0.01). Electrical pain thresholds increased and pain during suprathreshold stimulation decreased markedly on the stump and, to a lesser extent, on the contralateral limb after 1 month of treatment with amitriptyline or tramadol. Adverse effects were minor in all groups, but more common with tramadol.     

Online access to NDT for developing countries

As editors we want as many people to have access to NDT as possible.The last 18 months have seen a number of experimental initiativesto test the technical and logistical     

A method for assessing quality of control from glucose profiles.

AIM: As the practice of multiple assessments of glucose concentration throughout the day increases for people with diabetes, there is a need for an assessment of glycaemic control weighted for the clinical risks of both hypoglycaemia and hyperglycaemia. METHODS: We have developed a methodology to report the degree of risk which a glycaemic profile represents. Fifty diabetes professionals assigned risk values to a range of 40 blood glucose concentrations. Their responses were summarised and a generic function of glycaemic risk was derived. This function was applied to patient glucose profiles to generate an integrated risk score termed the Glycaemic Risk Assessment Diabetes Equation (GRADE). The GRADE score was then reported by use of the mean value and the relative percent contribution to the weighted risk score from the hypoglycaemic, euglycaemic, hyperglycaemic range, respectively, e.g. GRADE (hypoglycaemia%, euglycaemia%, hyperglycaemia%). RESULTS: The GRADE scores of indicative glucose profiles were as follows: continuous glucose monitoring profile non-diabetic subjects GRADE = 1.1, Type 1 diabetes continuous glucose monitoring GRADE = 8.09 (20%, 8%, 72%), Type 2 diabetes home blood glucose monitoring GRADE = 9.97 (2%, 7%, 91%). CONCLUSIONS: The GRADE score of a glucose profile summarises the degree of risk associated with a glucose profile. Values < 5 correspond to euglycaemia. The GRADE score is simple to generate from any blood glucose profile and can be used as an adjunct to HbA1c to report the degree of risk associated with glycaemic variability.