The binding of blood-borne estrogens in normal vegetarian and omnivorous women and the risk of breast cancer

Serial blood samples were taken at two-hour intervals over a 24-hour period from 25 premenopausal vegetarians (12 vegans and 13 ovolactovegetarians) and from 21 omnivorous controls. All members of the former group had been on a vegetarian diet for a minimum of three years. The mean proportion of estradiol unbound to blood proteins was similar in both vegetarians (1.26%) and meat eaters (1.16%). However, the amount bound to albumin was significantly raised in vegetarians (50.1% vs. 43.1%, p less than 0.009), whereas that bound to sex hormone-binding globulin (SHBG) was correspondingly lower (48.7% vs. 55.8%, p = 0.01). Mean levels of SHBG were similar in vegetarians (59.9 nmole/l) and omnivores (62.0 nmole/l), as was the total amount of free fatty acid (0.42 mmole/l for both). Within the vegetarian group, no differences were detected between vegans and ovolactovegetarians.     

Primary adenocarcinoma of the appendix

Thirteen cases of primary appendicular adenocarcinoma are reported. This rare tumour usually presents as acute appendicitis. The correct diagnosis is rarely entertained before or during surgery. The main treatment choice lies between appendicectomy alone and appendicectomy followed by right hemicolectomy. There are anatomical reasons for advising the latter and survival figures from the literature tend to support this preference. The cases reported here indicate that in the period 1972-1984, in the North West Region, there was a slight preference for appendicectomy alone. The additional procedure of right hemicolectomy did not confer any clear-cut survival advantage.     

Allosteric Modulators of Class B G-Protein-Coupled Receptors

Class B GPCR’s are activated by peptide ligands, typically 30-40 amino acid residues, that are involved in major physiological functions such as glucose homeostasis (glucagon and glucagon-like peptide 1), calcium homeostasis and bone turnover (parathyroid hormone and calcitonin), and control of the stress axis (corticotropin-releasing factor). Peptide therapeutics have been developed targeting these receptors but development of nonpeptide ligands, enabling oral administration, has proved challenging. Allosteric modulation of these receptors provides a potential route to developing nonpeptide ligands that inhibit, activate, or potentiate activation of these receptors. Here the known mechanisms of allosteric modulators targeting Class B GPCR’s are reviewed, particularly nonpeptide antagonists of the corticotropin-releasing factor 1 receptor and allosteric enhancers of the glucagon-like peptide-1 receptor. Also discussed is the potential for antagonist ligands to operate by competitive inhibition of one of the peptide binding sites, analogous to the Charniere mechanism. These mechanisms are then used to discuss potential strategies and management of pharmacological complexity in the future development of allosteric modulators for Class B GPCR’s.     

Mild gentamicin nephrotoxicity reduces the progression of chronic adriamycin nephrosis

SUMMARY: The effect of mild acute tubular injury on the progression of tubulointerstitial fibrosis was studied in pair-fed uninephrectomized male Wistar rats with established adriamycin nephrosis ( n = 34). Rats were stratified into three groups according to endogenous creatinine clearance (CrCl), proteinuria (Upr) and body weight (BW): (i) group 1 (Fe, n = 12) received a single intraperitoneal injection of ferric nitrilotriacetate (5 mg Fe/kg BW); (ii) group 2 (G, n = 10) three daily subcutaneous injections of gentamicin (60 mg/kg BW) and; (iii) group 3 (C, n = 12) saline injections. Serial CrCl (day 2, day 5, weeks 2, 4, 6 and 8) and renal histology (week 8) were examined following administration of nephrotoxin. CrCl was reduced on d2 (Fe: 0.78 ± 0.23 mL/min; mean ± SD) and day 5 (G: 0.91 ± 0.36 mL/min) as compared with C (1.22 ± 0.12 mL/min; P <0.05). There was no change in the serum creatinine and functional recovery occurred by d5 (Fe) and week 2 (G). Upr decreased transiently in G at week 2 (G: 482 ± 208 mg/day vs C: 716 ± 233; P = 0.05) despite similar food intake, baseline Upr and CrCl. At week 8, CrCl in Fe (0.84 ± 0.40 mL/min) was similar to C (0.84 ± 0.58 mL/min), whereas in G it remained stable (1.27 ± 0.39 mL/min; P <0.05). By morphometric analysis, mean relative interstitial volume (RIV) and glomerulosclerosis (GS) in Fe (RIV: 28.5 ± 13.4%; GS: 10.3 ± 12.3%) was no different to C (RIV: 24.5 ± 12.5%; GS: 20.9 ± 20.0%), whereas both parameters were reduced in G (RIV: 14.1 ± 8.1%; GS: 4.0 ± 4.8%; P <0.05). Mild gentamicin nephrotoxicity therefore reduced the progression of adriamycin nephrosis. the mechanism of this finding is unclear, but it may relate to altered glomerular and tubular cell handling of protein.     

Milk nasendoscopy in the assessment of dysphagia.

The bedside assessment of dysphagia may be difficult, due to the inability to witness the act of swallowing directly. The milk test described in this paper gives a good assessment of swallowing, is cheap and easily portable and allows an instant decision to be made without recourse to special investigations.     

Bell's palsy associated with IFN-alpha and ribavirin therapy for hepatitis C virus infection.

First-line therapy for hepatitis C virus (HCV) infection comprises interferon-alpha (IFN-alpha) and ribavirin for 6 or 12 months. Mild complications of therapy are common, but more serious complications are rare. Three patients with chronic HCV infection, acquired through injecting drug use, developed idiopathic facial paralysis (Bell's palsy) during therapy, with spontaneous resolution after withdrawal of treatment. Large-scale cohort studies reveal that IFNs are associated rarely with neurologic complications, and only one previous report has linked IFN-alpha therapy and Bell's palsy. We postulate that IFN-alpha therapy led to a breakdown of peripheral tolerance to myelin sheath antigens, leading to neuropathy, just as IFN-alpha therapy can cause autoimmune thyroiditis through breakdown of tolerance to native thyroid antigens.     

Traumatic or septic aortic regurgitation: diagnosis by oesophageal echocardiography

Severe aortic regurgitation was discovered in a young man 21 days after blunt chest trauma and after a prolonged febrile state with positive blood cultures. Using transoesophageal echocardiography (TEE), it was possible to make the differential diagnosis between traumatic rupture and endocarditis as the cause of valvular insufficiency. The use of TEE in the initial evaluation of severe thoracic trauma with an unclear clinical picture is recommended. This method is easy to use at the bedside and gives precise information on the aortic valve and the ascending aorta.