Role of substance P in suppressing growth hormone release in the rat.

To evaluate a possible physiological role of endogenous substance P (SP) in the control of growth hormone (GH; somatotropin) secretion, a specific antiserum against SP (anti-SP) was injected intraventricularly (3 microliters into the third cerebral ventricle) in unanesthetized unrestrained normal male rats. Control rats received an equivalent volume of normal rabbit serum (NRS). Intraventricular injection of the NRS lowered plasma GH concentrations significantly. The lowering was detected on first measurement at 10 min after injection and was maximal at 30 min. This was followed by a return toward the initial levels. Third ventricular injection of antiserum significantly increased plasma GH in comparison with control animals injected with NRS. The effect was observed within 10-20 min, and levels remained elevated for the 120-min duration of the experiment. To confirm the possible inhibitory role of endogenous SP on GH release, 3 microliters of 0.9% NaCl (saline) alone or saline containing a specific antagonist of SP, [D-Pro2,D-Trp7,9]SP, was injected into the third ventricle of normal male rats. The antagonist also increased plasma GH significantly (P less than 0.005) within 5 min compared with values in the saline-injected control group. Levels remained elevated for 30 min but had returned toward control values 60 min after injection. In contrast, synthetic SP significantly decreased plasma GH when injected intravenously or intraventricularly compared with plasma GH in the control saline-injected group. To investigate a possible direct action of SP on GH release from the anterior pituitary gland, we incubated synthetic SP with dispersed anterior pituitary cells for 1 hr. The release of GH from incubated anterior pituitary cells was not affected at any dose of SP (10(-9) to 10(-6) M) tested. These data strongly indicate that endogenous SP has a physiological inhibitory role in the control of GH secretion at the level of the hypothalamus in the male rat.     

Effects of erythromycin on Pseudomonas aeruginosa adherence to collagen and morphology in vitro.

The airways of patients with bronchiectasis and cystic fibrosis are often chronically colonised by Pseudomonas aeruginosa (PA), which is virtually impossible to eradicate. Low-dose erythromycin (EM), for unknown mechanisms, is efficacious in bronchiectasis and diffuse panbronchiolitis. In this study, an in vitro model to investigate PA adherence to human type IV basement collagen was developed by using scanning electron microscopy (SEM). There were significantly less PA bacilli per 20 random SEM fields (4,000x) when PA was cultured in 0.05, 0.5 and 5 microg x mL(-1) of EM compared with control (absence of EM). Adherence density (20 SEM fields x log(-1) inocular size) for PA obtained from no EM (56.8 +/- 43.16) was significantly higher than that obtained from 0.05, 0.5, and 5 microg x mL(-1) EM (21.5 +/- 17.56, 23.3 +/- 16.65, and 21.4 +/- 12.65 respectively). By using SEM it was found that PA, when incubated in EM (0.05, 0.5, 5 microg x mL(-1)) had a significant reduction in its diagonal length, radius, height, volume and surface area. It is possible, therefore, that these misshaped Pseudomonas aeruginosa bacilli are more susceptible to host defence mechanisms, while at the same time less adherent to the basement membrane of the airway in vivo. Therefore, this could help explain the clinical efficacy of low-dose erythromycin therapy on patients with Pseudomonas aeoruginosa infection.     

Clinical implications of increased plasma levels of CD8 in patients with hairy cell leukemia

Plasma levels of soluble T-suppressor/cytotoxic antigen (sCD8) were measured at diagnosis or before systemic treatment in 69 patients with hairy cell leukemia (HCL). The 49 nonsplenectomized patients were characterized by high concentrations of sCD8 antigen as compared with 17 controls (P less than .0001). The median sCD8 level in non- splenectomized patients was 1,050 U/mL (range: 160 to 2,400 U/mL) and was significantly higher (P less than .0001) than the median of 275 U/mL (range: 20 to 1,080 U/mL) in splenectomized patients. The relationship of sCD8 to clinical response to subsequent interferon alpha (IFN alpha) treatment was analyzed. Patients who showed subsequent hematologic response with normalization of all blood counts had significantly lower levels of sCD8 concentrations at diagnosis than those who did not (P = .0056). Furthermore, normalization of sCD8 during IFN alpha treatment paralleled the achievement of normal counts in peripheral blood, whereas soluble interleukin-2 receptor (sIL-2R) levels remained high in most patients after 12 to 15 months of treatment. We speculate that activation of suppressor/cytotoxic T cells might play a role in myelosuppression, and its modulation during treatment with IFN alpha correlates with normalization in peripheral blood counts.     

Cyclosporine and liver regeneration studied byin vivo 31P nuclear magnetic resonance spectroscopy

The changes in fructose-1-phosphate (F-1-P), intracellular pH, and ATP content of the liver after a fructose challenge were investigated noninvasivelyin vivo using phosphorus-31 nuclear magnetic resonance spectroscopy of dog liver four days after a portacaval shunt (PCS) with or without portal venous infusion of cyclosporin (CsA). The F-1-P metabolism was slower in PCS dogs (N=2) as compared to either the normal (N=2) or PCS+CsA-treated dogs (N=3) (P<0.05). The intracellular pH temporarily decreased from 7.3±0.05 to 7.0±0.05 during the fructose challenge. The regenerative indexes were increased in the PCS+CsA group (P<0.01). These data obtainedin vivo using³¹P-NMR spectroscopy in the liver following a portacaval shunt, suggest that : (1) the energy status of the liver and the metabolic response to fructose are reduced in PCS compared to normal animals and (2) CsA treatment enhances the regenerative response of the liver and prevents the reduction in hepatic function associated with portacaval shunting.Presented at the Proceedings of the International Meeting on Normal and Neoplastic Growth in Hepatology, Bari, Italy, June 1989.was supported, while in the US (1986–1989), by grants from: the C.N.R. (Italy, No. 203.4.11), the Council of International Exchange of Scholars (u.S.A., Fulbright Fellowship), and the Regione Veneto (Italy, Piano Sanitario Finalizzato Il Trapianto di Fegato).Supported in part by Regione Veneto and C.N.R. (Italy) grants, Fulbright Fellowship (U.S.), and by a research grant from the NIH (DK-29961).     

Self-expanding metallic stent in the treatment of colonic obstruction caused by advanced malignancies

INTRODUCTION: The treatment of malignant obstruction of the left colon or rectum usually requires emergency surgery on poor-risk patients, and the creation of a stoma is usually inevitable. With the use of self-expanding metallic stents, the prompt relief of large-bowel obstruction without surgery has become possible. This report describes our results in the use of self-expanding metallic stents in the treatment of left-sided colonic obstruction resulting from advanced malignancies. METHODS: From November 1997 to March 1999, insertion of self-expanding metallic stents was attempted in 24 patients with acute left-sided colonic obstruction caused by primary or recurrent malignancies. All the procedures were performed by colorectal surgeons. The guidewire was inserted through the channel of the endoscope, and its position was confirmed with fluoroscopy. Uncovered Wallstent® esophageal endoprostheses were used in all except the first case. The insertion and deployment of the stents were under both endoscopic and fluoroscopic guidance. RESULTS: There were 24 patients (15 males) with a mean age of 63.6 (range, 36–98) years. Thirteen patients had primary colorectal cancer and 11 had recurrent cancers (colorectal cancer, 5; gastric cancer, 5; other, 1). In the treatment of primary colorectal cancer, seven procedures were palliative, and no subsequent surgery was planned because of extensive liver metastasis or poor medical risk. The other six patients underwent elective resection after mechanical bowel preparation. There was no mortality related to the procedure. Stenting was successful in the relief of obstruction in 23 patients. Perforation of the colon occurred in one patient, and an emergency Hartmann's operation was performed. Migration of the stents occurred in three patients. Only 3 of the 18 patients in the palliation group required the subsequent creation of stomas. CONCLUSION: The use of the self-expanding metallic stents can achieve rapid and effective nonsurgical means to relieve left-sided colonic obstruction. It provides good palliation for unresectable advanced tumors that cause colonic obstruction. It may also have a role in the temporary relief of obstruction so that subsequent colonic resection can be performed under elective conditions.Poster presentation at The American Society of Colon and Rectal Surgeons' 100th Anniversary and Tripartite Meeting, Washington, D.C., May 1 to 6, 1999.     

Lower risk of tuberculosis in obesity

BACKGROUND: Obesity is increasingly prevalent in both developed and developing areas. Although undernutrition is well associated with tuberculosis, few studies have systematically examined the association with obesity. Method A cohort of 42 116 individuals 65 years or older enrolled at 18 health centers for elderly patients in Hong Kong, China (which has a tuberculosis incidence of approximately 90 per 100,000 population), in 2000 were followed up prospectively through the territory-wide tuberculosis registry for the development of active tuberculosis from 3 months after enrollment until December 31, 2005, using the identity card number as the unique identifier. The association with body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters), as categorized by the Asian standards, was assessed with the control of other baseline characteristics. RESULTS: Obese (BMI>or=30) and overweight (BMI, 25 to <30) individuals were at significantly lower risks of developing active tuberculosis than normal-weight individuals (BMI, 18.5 to <25), with hazard ratios (95% confidence intervals) of 0.36 (0.20-0.66) and 0.55 (0.44-0.70), respectively, after adjustment for baseline demographic, social, and clinical variables. An inverse linear association was observed predominantly for pulmonary but not extrapulmonary tuberculosis. This association persisted after controlling for potential confounders or excluding individuals with known tuberculosis risk factors. CONCLUSIONS: Obesity is associated with a lower risk of active pulmonary tuberculosis in the older population of Hong Kong. The presence of such a strong but selective association across the whole spectrum of BMI could have major biological, clinical, and/or epidemiological implications. Further studies are indicated to explore the underlying mechanisms, potential clinical utilities, and possible epidemiological consequences.     

An indolent case of severe acute respiratory syndrome

Severe acute respiratory syndrome (SARS) is a highly contagious and typically rapidly progressive form of atypical pneumonia, which spread from Asia to many parts of the world in early 2003. Clinical diagnosis of SARS requires the presence of unremitting fever and progressive pneumonia despite antibiotic therapy, particularly in the presence of lymphopenia and raised transaminase levels. We report the case of a woman who had undergone a successful allogeneic bone marrow transplant for acute myeloid leukemia. She presented initially with fever and a normal chest radiograph. Her indolent clinical course of SARS was punctuated by resolution of fever, but there was progressive radiologic deterioration and increasing serum antibody titer against SARS coronavirus. Treatment with oral prednisolone and ribavirin normalized her lymphopenia, altered transaminases, chest radiograph and high-resolution computed tomography appearances rapidly. Our experience should alert other clinicians in recognizing this atypical indolent presentation of SARS, to protect health care workers and the community at large and to ensure that these patients are properly treated.