NIFEDIPINE BLOCKS ACTH AND CORTISOL RELEASE IN MAN

1. The present study investigated the effect of prior administration of nifedipine on AVP-induced ACTH release in seven normal volunteers. Three protocols were used: 20 mg oral nifedipine; 0.14 pressor units intramuscular (i.m.) per kg bodyweight aqueous AVP; oral nifedipine plus i.m. AVP 90 min later. Plasma ACTH and cortisol were measured at intervals for 2.5 h during each test. 2. The mean peak plasma ACTH and cortisol levels and the mean peak changes from basal in these levels were significantly lower in the nifedipine/AVP test than in the AVP alone test. The integrated area under the cortisol time curve was significantly lower for the nifedipine/AVP test than that for the AVP test alone. Nifedipine alone caused no changes in ACTH or cortisol. 3. Acute administration of oral nifedipine caused an inhibition of AVP-stimulated ACTH and cortisol release in normal humans. This effect may be due to blockade of plasma membrane calcium channels normally activated during AVP stimulation of pituitary corticotrophs.     

CROHN'S DISEASE: A COLON AND RECTAL DEPARTMENT EXPERIENCE

This study reviewed a series of patients with Crohn's disease managed by surgeons of the Department of Colon and Rectal Surgery, St Vincent's Hospital, Melbourne, since 1978. There were 306 patients: 171 males and 135 females. The mean age at diagnosis was 33.4 years (range 11–93). The distribution of the disease was small bowel 32.3%, small bowel and colon 26.5%, colon 39.9%, and anal disease alone 1.6%. A total of 416 abdominal operations were performed on 204 patients. The commonest indications for surgery were failed medical therapy (21.9%), small bowel obstruction (15.9%), enteric tistula (10.1%), and intra-abdominal abscess (10.1%). The most frequently performed procedures were ileocolic resection with anastomosis (28.8%), small bowel resection (9.4%), and total colectomy and ileostomy (7.0%). Postoperative complications included anastomotic leaks in 4.0%. intra-abdominal abscess formation in 3.6%, and enterocutaneous fistulae developed in 6%. Three patients died during the review period. During follow up (mean 84.4). 30% of patients developed recurrence requiring further surgery at a mean of 72.7 months postoperatively. The most frequent site for a recurrence was the pre-anastomotic terminal ileum (61.7%). In conclusion. the majority of patients with Crohn's disease will require resectional surgery at some stage. This can be performed with a low mortality and morbidity, and a recurrence rate of around 5% per year.     

Postprandial acid reflux is reduced by delayed gastric emptying.

The aim of this study was to investigate influence of delayed gastric emptying on postprandial reflux in esophageal pH. Sixty-nine consecutive patients underwent 24 hour (h) esophageal pH monitoring and gastric emptying. In 24 h esophageal pH monitoring, % postprandial reflux pH<4 for 2 h after each meal (% PRT) was extracted from the 24 h pH profile. After solid test meal (1 mCi, Tc99m) was given, gastric emptying was measured with a gamma detector placed transnasally 5 cm below lower esophageal sphincter. % PRT was similar among the 34 normal, 26 delayed and 9 rapid gastric emptying rate patients. Thirty-five with a positive pH study and 34 with a negative had a similar prevalence of gastric emptying disorder. In the positive pH study group, patients with normal gastric emptying had significantly higher % PRT than those with delayed gastric emptying (22.0 vs 12.1%, P<0.05). In the same population, patients with a normal %PRT had a significantly higher prevalence of delayed gastric emptying compared with those with a positive % PRT (6/8 vs 9/27, P<0.05). In patient with abnormal acid exposure but normal % PRT on 24 h esophageal pH monitoring, gastric emptying may be delayed.     

Pharmacokinetic characterization in xenografted mice of a series of first-generation mimics for HLA-DR antibody, Lym-1, as carrier molecules to image and treat lymphoma.

Despite their large size, antibodies (Abs) are suitable carriers to deliver systemic radiotherapy, often molecular image-based, for lymphoma and leukemia. Lym-1 Ab has proven to be an effective radioisotope carrier, even in small amounts, for targeting human leukocyte antigen DR (HLA-DR), a surface membrane protein overexpressed on B-cell lymphoma. Pairs of molecules (referred to as ligands), shown by computational and experimental methods to bind to each of 2 sites within the Lym-1 epitopic region, have been linked to generate small (<2 kDa) molecules (referred to as selective high-affinity ligands [SHALs]) to mimic the targeting properties of Lym-1 Ab. METHODS: A lysine-polyethylene glycol (PEG) backbone was used to synthetically link 2 of the following ligands: deoxycholate, 5-leuenkephalin, triiodothyronine, thyronine, dabsyl-L-valine, and N-benzoyl-L-arginyl-4-amino-benzoic acid to generate a series of 13 bidentate SHALs with a biotin or 1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid (DOTA) chelate attached to the linker. These SHALs have been assessed for their selectivity in binding to HLA-DR10-expressing cells and for their pharmacokinetics and tissue biodistribution in mice. Biotinylated versions of these SHALs discriminated cell lines positive for HLA-DR10 expression with near-nanomolar affinity. The DOTA versions of 4 SHALs were labeled with (111)In for pharmacokinetic studies in mice with HLA-DR10-expressing malignant Raji xenografts. RESULTS: The bidentate, biotinylated, and DOTA-SHALs were synthesized in high-purity, multimilligram amounts. Mean radiochemical and product yields and purities were 90%, 75%, and 90% at mean specific activities of 3.9 MBq/microg (105 microCi/microg) for the (111)In-labeled SHALs. As expected, rapid blood clearance and tumor targeting were observed. The pharmacokinetics of the SHALs was influenced by the component ligands. Biliary clearance, kidney localization, and serum receptor binding contributed to less favorable tumor targeting. CONCLUSION: A series of SHALs was readily synthesized in multimilligram amounts and showed the expected selective binding in vitro. Better selection of the SHAL components should provide second-generation SHALs with improved properties to fulfill the substantial potential of these novel molecular carriers for targeting.     

Responses to questions by medical students about family practice

Medical students frequently have questions about the specialty of family practice. Responses to 30 questions commonly asked about family practice are presented with a review of recent literature. These responses may assist medical students and their advisors in considering the choice of family practice as a career.     

Magnetization Transfer and T2 Relaxation Components in Tissue

T₂ relaxation makes an important contribution to tissue contrast in magnetic resonance (MR) imaging. Many tissues are known to exhibit multicomponent T₂ relaxation that suggests some compartmental segregation of mobile protons on a T₂ timescale. Magnetization transfer (MT) is another relaxation mechanism that can be used to produce tissue contrast in MR imaging. The MT process depends strongly on water-macromolecular interactions. To investigate the relationship between multicomponent T₂ relaxation and the MT process, multiecho T₂ measurements have been combined with MT measurements for freshly excised samples of cardiac muscle, striated muscle, and white matter. For muscle, short T₂ components show greater MT than long T₂ components, consistent with the belief that they represent distinct water environments. For white matter, quantitative MT measurements were identical for the two major T₂ components, apparently because of exchange between the T₂ compartments on a timescale characteristic of the MT experiment. Implications for accurate modeling of MT in tissue and the use of MT for MR image contrast are discussed.     

Three Evaluation Methods of a Community Health Advocate Program

The title Community Health Advocate (CHA) is one of thirty or more titles used throughout the world for an indigenous outreach worker who is trusted and respected in his or her community and who serves as a bridge between peers and health professionals. In 1992, the Center for Healthy Communities in Dayton, Ohio developed a program to train as Advocates people indigenous to the communities in which they would be working. Since the first CHAs began work in January 1993, the effectiveness of the program has been evaluated from three perspectives: the Community Health Advocates, the managers directors of the community sites at which the CHAs work, and the clients with whom the CHAs work. Advocates indicated that the training program adequately prepared them for their roles and functions. They also identified systematic frustrations and barriers that made it more difficult for them to perform their job. Community site directors and community leaders indicated that the CHAs were considered a positive force in meeting client needs and facilitating independence, and were very effective in outreach and coordination of resources. A survey of CHA clients revealed an overwhelmingly positive response to the Advocate's work, validating the belief that CHAs can fill an important niche in the health care community. The three evaluation processes described in this paper helped to document the need for and the effectiveness of this program and can serve as a model for similar programs.     

Diffuse Nodular Regenerative Hyperplasia of the Liver Associated with Human Immunodeficiency Virus and Visceral Leishmaniasis

We present a patient with human immunodeficiency virus (HIV) infection coincident with diffuse nodular regenerative hyperplasia (DNRH) of the liver and visceral leishmaniasis. This association has not been previously described. Some DNRH cases are secondary to irregular blood flow in the liver. In the presently described case, there exist two possible conditioning factors for heterogenous distribution of blood flow: 1) the increased blood flow from splenomegaly, and 2) the irregular circulation of blood through sinusoids infiltrated by Leishmania -parasitized hyperplastic macrophages.