Proximal tubular function in dogs with thoracic caval constriction.

The effect of saline infusion on proximal sodium reabsorption was compared in normal dogs and in dogs with acute or chronic partial thoracic vena cava obstruction. After acute vena cava obstruction, proximal fractional sodium reabsorption rose by 74%. During continued caval obstruction, saline loading strikingly reduced proximal reabsorption but sodium excretion remained minimal. In chronic caval dogs, saline loading reduced proximal fractional sodium reabsorption by 31% but sodium excretion in the micropunctured kidney was only 41 muEq/min. After saline infusion in normal dogs, proximal fractional sodium reabsorption fell 39% while unilateral sodium excretion rose to 584 muEq/min. Nephron filtration rate was also measured before and after saline loading in normal and chronic caval dogs in both repunctured and fresh tubules. There was a marked increase in nephron filtration rate in repunctured tubules and no change in freshly punctured tubules in both groups. The effect of saline loading on nephron filtration rate in normal and chronic caval dogs was similar, therefore, whether repunctured or fresh nephrons were considered.We conclude that saline infusion depresses proximal sodium reabsorption in acute and chronic TVC dogs. Since saline loading markedly increases distal delivery without a concomitant natriuresis, enhanced distal reabsorption must play a major role in the sodium retention exhibited by chronic caval dogs. Redistribution of filtrate does not appear to be a factor in this sodium retention.

Tubular reabsorption of sodium during acute and chronic volume expansion in man.

Renal hemodynamics and tubular fractional sodium reabsorption (FSR) were evaluated by clearance techniques during acute and chronic extracellular volume expansion in man. (1 - V/GFR) x 100 was used as an index of proximal and (C(H2O)/V) x 100 as an estimate of distal fractional reabsorption. After acute loading with isotonic saline 37 ml/kg body wt, proximal FSR decreased by 4.8% and distal FSR decreased by 4.4%. After comparable chronic expansion by mineralocorticoids ("escape"), proximal FSR also decreased by 3.9%, but distal reabsorption was not altered.In separate studies, subjects were progressively infused with saline to 57 (E(1)) and to 80 (E(2)) ml/kg body wt, and appeared to divide into "excreters" (maximum U(Na)V > 1000 muEq/min) and "nonexcreters" (maximum U(Na)V < 550 muEq/min). In the excreters, GFR rose, proximal FSR decreased by 7.1% after E(1) and only 0.9% further after E(2). Distal FSR fell by 14.8% after E(1) and by an additional 4.9% after E(2). In the nonexcreters, GFR was stable and proximal FSR did not fall significantly after E(1) or E(2). Distal FSR decreased 4.5% after E(1) and 1.3% further after E(2). It is concluded that both acute and chronic extracellular expansion decrease proximal FSR in man, but only acute loading depresses distal FSR. Ability of some men to excrete sodium rapidly after acute infusion is related to larger increases in GFR and greater decreases in both proximal and distal FSR than occur in men in whom natriuresis is more limited.

Induction of rat hepatic glucocorticoid-inducible cytochrome P450 3A by metyrapone.

The bipyridyl compound metyrapone is a potent inhibitor of cytochromes P450, a gene superfamily of haemoproteins involved in the metabolism of many xenobiotics as well as endogenous compounds such as steroid hormones. Administration of metyrapone to male rats induces the expression of the cytochrome P450 sub-family 3A (CYP3A). In order to determine whether metyrapone was causing the induction of CYP3A by blocking endogenous glucocorticoid metabolism, CYP3A levels were examined in rat hepatocytes cultured in serum-free medium supplemented with hydrocortisone 21-hemisuccinate plus or minus metyrapone. Western blotting indicated that metyrapone alone induces CYP3A and that hydrocortisone 21-hemisuccinate is ineffective. However, hydrocortisone 21-hemisuccinate enhanced the levels of CYP3A induced by metyrapone. In contrast, glucocorticoid-inducible tyrosine aminotransferase (TAT) activity was unaffected by metyrapone but metyrapone enhanced the levels induced by hydrocortisone 21-hemisuccinate. An examination of the metabolism of hydrocortisone by rat hepatocytes in vitro indicated that metyrapone perturbed the catabolism of hydrocortisone under conditions which give rise to an enhancement of hydrocortisone 21-hemisuccinate and hydrocortisone-dependent TAT induction. However, evidence is presented to suggest that such a perturbation of hydrocortisone metabolism could not account for the glucocorticoid potency amplifying property of metyrapone. Thus the induction of CYP3A and the enhancement of glucocorticoid-mediated TAT induction appears not to be associated with any perturbation in glucocorticoid metabolism but with some other as yet undefined mechanism(s).

Pharmacologic management of cancer pain in rural Minnesota.

Use of analgesic medications for cancer pain was assessed in six Minnesota communities. In our survey, cancer patients were treated primarily by family practice physicians. Approximately 70% were given one or more analgesics; 84% received a nonsteroidal antiinflammatory drug and 73% received an opioid. Most patients given an antiinflammatory drug received less than the maximal recommended dose for the drug. The most common opioid for cancer pain was oral morphine. Approximately 40% of the patients treated with opioids took the drug only when needed; the remainder took the drug around-the-clock, with or without additional opioids for breakthrough pain. Only 14% of patients who received analgesics received a coanalgesic and only 13% received a nonanalgesic adjuvant. The patterns of analgesic use in these communities corresponded well with accepted principles of cancer pain management: liberal use of opioids, use of oral morphine as the predominant agent, and avoidance of meperidine and opioid agonist/ antagonists.

Effectiveness of occlusion therapy in ametropic amblyopia: a pilot study.

AIMS/BACKGROUND: To examine the relative contributions of non-specific (for example, spectacle correction) and specific (that is, occlusion therapy) treatment effects on children with ametropic amblyopia. To assess the importance and practicality of objectively confirming the prescribed occlusion dose. METHODS: Subjects were entered into a two phase trial. In the first ('pretreatment') subjects were provided with spectacle correction and underwent repeat visual acuity (VA) and contrast sensitivity (CS) testing until acuity in their amblyopic eye had stabilised. Subjects then progressed to the second phase ('treatment') in which they underwent direct, unilateral occlusion for 1 hour per day for 4 weeks. Patching was objectively monitored using an occlusion dose monitor. RESULTS: Eight subjects completed the trial, all but one of whom achieved > 80% concordance with the occlusion regimen. Within the pretreatment phase, mean amblyopic eye VA improved by 0.19 log units (p = 0.008) while mean CS gained 0.09 log units (p = 0.01). An identical improvement in mean VA was recorded in the fellow eyes (p = 0.03) while mean CS gained 0.11 log units (p = 0.02). Within the treatment phase, mean VA further improved (0.12 log units, p = 0.009) although this gain had halved by the end of treatment and was no longer statistically significant (p = 0.09). CONCLUSIONS: Visual performance improved significantly during pretreatment whereas further gains seen during occlusion were not sustained. Evaluation of occlusion regimens must take into consideration the potentially confounding influence of 'pretreatment effects' and the necessity to confirm objectively the occlusion dose a child receives.

Compliance in amblyopia therapy: objective monitoring of occlusion.

AIM/BACKGROUND: This study aimed to determine the feasibility of objective compliance monitoring of amblyopia therapy in clinical research. Occlusion has been the mainstay of amblyopia therapy for over 250 years, yet it has never been subjected to rigorous evaluation. Treatment regimens range arbitrarily from a few minutes to most of the waking hours of the day. Compliance is problematic and as, hitherto, accurate objective monitoring has been impossible it is not known how much occlusion is required to effect an improvement in vision. METHODS: An occlusion dose monitor (ODM) has been developed. The ODM consists of a modified occlusion patch and a miniature battery driven datalogger which periodically monitors patch skin contact. The patch is a standard disposable item with two miniature electrocardiogram electrodes attached to its undersurface. The datalogger comprises a high speed static RAM and a clock driven address counter. Data are retrieved using an IBM PC/AT computer. Fifteen child amblyopes were randomly allocated unilateral occlusion of 1, 4, or 8 hours per day for 4 weeks. Owing to data loss, presumed because of accumulation and discharge of static electricity, an additional child was included in the 8 hour group. Outcome measures were objective (ODM) and subjective (diary) compliance with treatment, logMAR visual acuity, and contrast sensitivity. RESULTS: Objective monitoring of occlusion is technically feasible and clinically informative. CONCLUSION: Objective monitoring of occlusion has opened up new research opportunities which, it is hoped, will enable the dose-effect relation of occlusion therapy in the various types of amblyopia to be investigated objectively, and facilitate the design of effective therapeutic regimens.

The detection of a population of submillimeter-bright, strongly lensed galaxies.

Gravitational lensing is a powerful astrophysical and cosmological probe and is particularly valuable at submillimeter wavelengths for the study of the statistical and individual properties of dusty star-forming galaxies. However, the identification of gravitational lenses is often time-intensive, involving the sifting of large volumes of imaging or spectroscopic data to find few candidates. We used early data from the Herschel Astrophysical Terahertz Large Area Survey to demonstrate that wide-area submillimeter surveys can simply and easily detect strong gravitational lensing events, with close to 100% efficiency.

Testicular carcinoma.

Testis cancer is most commonly discovered because of painless testicular enlargement. Careful examination remains the best non-invasive diagnostic procedure. Accurate definition of pathological type and clinical stage determines management and defines prognosis. Surgical removal of the testis by an inguinal incision after spermatic cord occlusion is mandatory, and scrotal needling or biopsy must be avoided. Seminomas are the most common. When confined to the testis or when spread is limited to a few small retroperitoneal nodes, cure rates of 90% or more are produced by orchiectomy and radiation. Non-seminomatous germinal tumors should be staged surgically using retroperitoneal lymphadenectomy if clinical staging implies minimal tumor spread. Where tumor spread is found, aggressive chemotherapy produces a cure rate of greater than 95%. For advanced disease, chemotherapy is the primary treatment post-orchiectomy.

Peripheral neuropathy with sympathetic overactivity from industrial contact with acrylamide.

This paper describes the experimental and clinical findings of acrylamide intoxication in a human being. It is believed that this is the first such case to be recorded in the medical literature.Acrylamide is widely used as a "chemical grout". It is pumped into dirt, clay and stone walls of excavations in a liquid state together with a catalyst, and it then polymerizes to make a watertight shield.This chemical is neurotoxic in its non-polymerized form and can be absorbed through the intact skin, mucous membranes and lungs. In spite of warnings with regard to its handling, this worker became careless, and developed a contact dermatitis and a polyneuropathy with bluish cold extremities which dripped perspiration.In six months' time after his removal from contact with the chemical the patient made a complete clinical recovery. He was advised not to work with the chemical.

Local recurrence of adenocarcinoma of the rectosigmoid. Is postoperative adjuvant radiotherapy justified?

Adjuvant postoperative radiation therapy has been suggested for adenocarcinoma of the rectum and sigmoid colon to reduce the incidence of local recurrences. Determination of this incidence is necessary to optimally employ such adjuvant therapies. Ninety-nine patients with adenocarcinoma of the rectum or sigmoid who had surgery from 1976-1984 were reviewed. Follow-up ranged from one to eight years (average 4.1 years). Twenty-three patients had gross unresected residual tumor due to local invasion. Fifteen of the remaining 76 have developed recurrences (20 percent). Two patients (2.6 percent) had local recurrences without concurrent regional or distant metastases. Thus local recurrences rarely are encountered without concurrent regional or distant metastases. Therefore, postoperative radiation therapy to prevent local recurrences is not justified, given the small number of patients potentially benefited. Treatment modalities will need to address regional and distant metastases in addition to local recurrences.

Reliability of visual acuity in children with reduced vision.

We examined the test-retest reliability of visual acuity in 18 children referred to the Hospital Eye Service with reduced vision. Unaided distance acuities were recorded, using logarithmically scaled letter charts, on two occasions separated by an interval of one week during which no clinical intervention took place. Coefficients of repeatability were found to be +/- 0.25 and +/- 0.21 log units in left and right eyes, respectively. A further analysis of 14 subjects' data each of whom had one eye with consistently poorer acuity in both test sessions yielded coefficients of repeatability of +/- 0.15 and +/- 0.22 log units in, respectively, the better and poorer eyes. The reliability of visual acuity recorded in the better eye closely approximates to that previously found in normal adults, whilst that of the poorer eye appears more comparable to that of adult clinical populations.

Cystitis associated with tiaprofenic acid.

Ten patients with cystitis associated with tiaprofenic acid were reviewed. All patients displayed similar cystoscopic and histological features, and all failed a variety of initial therapies but achieved a dramatic improvement or resolution of symptoms with discontinuation of the tiaprofenic acid. Drug-induced cystitis may be more common than previously recognized.

The effect of pupil dilation with tropicamide on vision and driving simulator performance.

PURPOSE: To assess the effect of pupil dilation on vision and driving ability. METHODS: A series of tests on various parameters of visual function and driving simulator performance were performed on 12 healthy drivers, before and after pupil dilation using guttae tropicamide 1%. A driving simulator (Transport Research Laboratory) was used to measure reaction time (RT), speed maintenance and steering accuracy. Tests of basic visual function included high- and low-contrast visual acuity (HCVA and LCVA), Pelli-Robson contrast threshold (CT) and Goldmann perimetry (FIELDS). Useful Field of View (UFOV--a test of visual attention) was also undertaken. The mean differences in the pre- and post-dilatation measurements were tested for statistical significance at the 95% level using one-tail paired t-tests. RESULTS: Pupillary dilation resulted in a statistically significant deterioration in CT and HCVA only. Five of 12 drivers also exhibited deterioration in LCVA, CT and RT. Little evidence emerged for deterioration in FIELDS and UFOV. Also, 7 of 12 drivers appeared to adjust their driving behaviour by reducing their speed on the driving simulator, leading to improved steering accuracy. CONCLUSIONS: Pupillary dilation may lead to a decrease in vision and daylight driving performance in young people. A larger study, including a broader spectrum of subjects, is warranted before guidelines can be recommended.