The glomerulo-tubular junction: a target in renal diseases

Both global and segmental glomerulopathies may damage specific areas of the renal glomerulus. Diseases associated with glomerular hyperperfusion cause lesions at the vascular pole, while diseases associated with proteinuria often damage the tubular pole. Atubular glomeruli are now known to be plentiful in a variety of common renal diseases. These glomeruli are disconnected from their tubule at the tubular pole and therefore cannot participate in the production of urine. It is widely believed that the disconnection is a result of external compression by periglomerular fibrosis. However, the variable anatomy and cell populations within both the glomerulus and the beginning of the proximal tubule at the glomerulo-tubular junction may also have important roles to play in the response to damage at this sensitive site of the nephron.     

Dilemmas, ethics and intent--a commentary

Responding to a preceding article by Michael J. Newton ("Moral dilemmas in surgical training: intent and the case for ethical ambiguity"), Downie comments on three of Newton's themes. He agrees that trainees should engage in ethical self-appraisal but cautions that introspection is inappropriate at the time of an operation. Regarding Newton's downplaying of philosophical analysis in medical ethics, Downie agrees that there are limitations to the philosophical approach but contends that it can serve a very worthwhile function in helping doctors deal with ethical uncertainties. Finally, Downie perceives ambiguities in Newton's emphasis on the central importance of "ethical intent," which rejects the idea of ethical standards while urging individuals to take "personal responsibility" for their actions.     

Alpha-adrenergic agents in urinary disorders of the proximal urethra. Part II. Urethral obstruction due to "sympathetic dyssynergia".

Lower urinary tract obstruction in patients with neurological lesions can be due to "sympathetic dyssynergia". The obstruction can be at the level of the external sphincter. Phentolamine (i.v.) used during the voiding cystourethrogram helps to make the diagnosis. Phenoxybenzamine therapy produced improvement in 10 of 18 patients. As a rule, patients had to continue on the drug to maintain their response.     

Observations on Nine Personal Cases Where Esophagitis Has Appeared as a Complication of a Functioning Vertical Gastroplasty

This paper is based on observations on a personal series of patients who presented with severe ulcerating esophagitis, unresponsive to medical treatment following a vertical stapled gastroplasty. With one exception this was a late complication in an effective weight loss procedure. The therapeutic modalities chosen to treat this problem depended on patient choice, as well as personal experience with treating earlier cases. Unfortunately, I could find little guidance in the literature or from my colleagues on how to treat this problem. Conversion to a Roux-Y gastric bypass seemed the most satisfactory solution to the problem, relieving the symptoms and maintaining the weight loss.     

Are universities preparing nurses to meet the challenges posed by the Australian mental health care system?

The preparedness of comprehensive nurses to work with the mentally ill is of concern to many mental health professionals. Discussion as to whether current undergraduate nursing programs in Australia prepare a graduate to work as a beginning practitioner in the mental health area has been the centre of debate for most of the 1990s. This, along with the apparent lack of interest and motivation of these nurses to work in the mental health area following graduation, remains a major problem for mental health care providers. With one in five Australians now experiencing the burden of a major mental illness, the preparation of a nurse who is competent to work with the mentally ill would appear to be a priority. The purpose of the present study was to determine third year undergraduate nursing students' perceived level of preparedness to work with mentally ill clients. The results suggested significant differences in students' perceived level of confidence, knowledge and skills prior to and following theoretical and clinical exposure to the mental health area. Pre-testing of students before entering their third year indicated that the philosophy of comprehensive nursing: integration, although aspired to in principle, does not appear to occur in reality.     

Effect of anesthetics on reflex micturition in the chronic cannula-implanted rat

It is well known that urethane is a suitable anesthetic for acute studies and has been extensively recommended for investigations related to micturition physiology. This is mainly because of the capability of urethane anesthesia to spare reflex micturition as well as its easily established long-lasting and stable anesthetic level. However, urethane anesthesia is usually restricted to acute experiments due to its potential toxicity. This study searched for an alternative to urethane that would be suitable for studies in which recovery from anesthesia was needed. The list of administered drugs was as follows: pentobarbital, thiobutabarbital, ketamine-acepromazine, ketamine-diazepam, tiletamine-zolazepam, fentanyl-droperidol, alphaxalone-alphadolone, propofol, isoflurane, methoxyflurane, azaperone, tribromoethanol, and buprenorphine. Among these drugs, only tiletamine-zolazepam spared the reflex micturition contractions. However, the duration of this anesthesia was too short (approximately 30 minutes) to complete the necessary testing and additional dosing of the anesthetic generally obliterated the micturition reflex. On the other hand, rats given i.v. urethane infusion (10% solution in 0.9% saline, 3.2-4.0 mg/kg/min, total dose 0.56-1.03 g/kg) maintained a stable anesthesia that permitted both reflex micturition and stereotaxic procedures. Rats moved spontaneously 3-16 hours after cessation of i.v. urethane anesthesia and completely recovered in 2 days without significant after-effects. Bladder function was normal. No pathological changes were seen 1 week later. The present results suggest that urethane is the most suitable anesthetic for acute and chronic physiological experiments that require demonstration of reflex micturition. Neurourol. Urodynam. 19:87-99, 2000.     

Effects of thiopental and its optical isomers on nicotinic acetylcholine receptors

BACKGROUND: With the exception of gamma-aminobutyric acidA (GABAA) receptors, the major molecular targets underlying the anesthetizing actions of thiopental have yet to be established. Neuronal nicotinic acetylcholine receptors (nAChRs) are closely related to GABAA receptors and hence might also be major targets. If so, they might be expected to be substantially inhibited by surgical concentrations (EC50 = 25 micrometer) of thiopental and to display the same stereoselectivity as does general anesthesia. METHODS: Neuronal alpha4beta2, neuronal alpha7 and muscle alphabetagammadelta nAChRs were expressed in Xenopus oocytes. Peak acetylcholine-activated currents were measured at -70 mV using the two-electrode voltage clamp technique. Racemic thiopental and its two optical isomers were applied with and without preincubation and at high and low concentrations of acetylcholine. RESULTS: Inhibition of all three nAChRs was enhanced by preincubation with thiopental, a protocol that mimics the pharmacologic situation in vivo. Using this protocol, inhibition was further enhanced by high concentrations of acetylcholine, with IC50 = 18 +/- 2, 34 +/- 4, and 20 +/- 2 micrometer (mean +/- SEM) thiopental for the neuronal alpha4beta2, neuronal alpha7 and muscle alphabetagammadelta nAChRs, respectively, with Hill coefficients near unity. Neither the neuronal alpha7 nor the muscle alphabetagammadelta nAChR differentiated between the optical isomers of thiopental. However, R(+)-thiopental was significantly more effective than the S(-) isomer at inhibiting the neuronal alpha4beta2 nAChR; interestingly, this is diametrically opposite to their stereoselectivity for general anesthesia. CONCLUSIONS: Both central neuronal and peripheral muscle nAChRs can be substantially inhibited by thiopental at surgical EC50 concentrations but with either no stereoselectivity or one opposite to that for general anesthesia. Thus, nAChRs are probably not crucial targets for producing thiopental anesthesia, although nAChRs may play a part in the side effects produced by this agent.     

Cell necrosis and endocytosis (apoptosis) in an embryonal rhabdomyosarcoma of the orbit

An orbital embryonal rhabdomyosarcoma, which was excised from the orbit of an 8-year-old girl, was studied by light microscopy and transmission electron microscopy. Cells within the tumour demonstrated by light microscopy diffuse areas of necrosis and isolated single-cell necrosis. There were many viable tumour cells with intracytoplasmic vacuolar structures which contained basophilic granules. Ultrastructural studies showed close apposition between well-preserved tumour rhabdomyoblasts and degenerate or necrotic tumour cells: degenerate cells and condensed cell fragments were observed within the cytoplasm of the well-preserved tumour cells. Some cells which showed degenerative changes had features which suggested that they had ingested more than one degenerate cell on separate occasions. This phenomenon may be regarded as a variant of selective individual cell death, currently referred to as apoptosis, which has not been previously reported in a case of embryonal rhabdomyosarcoma. The patient remains free of tumour recurrence four years following treatment with combined radiotherapy and chemotherapy.