Association between in utero zidovudine exposure and nondefect adverse birth outcomes: analysis of prospectively collected data from the Antiretroviral Pregnancy Registry.

OBJECTIVE: To examine the association between nondefect adverse birth outcomes and in utero exposure to zidovudine (ZDV)-containing regimens versus non-ZDV antiretroviral (ARV) regimens. DESIGN: Analysis of prospectively-collected data. SETTING: Global. POPULATION: HIV-infected pregnant women prenatally exposed to antiretrovirals. METHODS: Estimation of prevalence of and risk for nondefect adverse birth outcomes among HIV-infected women. MAIN OUTCOME MEASURES: Prevalence of and risk for nondefect adverse birth outcomes. RESULTS: Among 12 780 singleton birth outcomes with in utero ZDV exposure, 96.1% were live births; 3.9% were spontaneous abortions, induced abortions or stillbirths. Among live births, 16.4% were low birthweight (LBW); 12.3% were premature. Among 1904 outcomes with in utero exposure to non-ZDV ARV regimens, 85.8% were live births; 14.2% were spontaneous abortions, induced abortions or stillbirths. Among live births, 14.1% were LBW; 12.4% were premature. Relative risk comparing exposure to ZDV-containing ARV regimens to non-ZDV ARV regimens for spontaneous abortions was 0.18 (95% confidence interval [95% CI] 0.14-0.22); induced abortions 0.28 (95% CI 0.22-0.36); stillbirths 0.76 (95% CI 0.51-1.12); premature births 1.00 (95% CI 0.87-1.15) and LBW 1.17 (95% CI 1.02-1.33). CONCLUSION: Prevalence of nondefect adverse birth outcomes is lower among outcomes with in utero ZDV exposure versus in utero non-ZDV ARV exposure. The risks for spontaneous and induced abortions were no different for ZDV-containing regimens versus non-ZDV ARV regimens. For premature births and stillbirths, there was no significant difference in risk between the two regimens. The risk of LBW was statistically significantly higher among ZDV-containing regimens versus non-ZDV ARV regimens. TWEETABLE ABSTRACT: ZDV-containing regimens do not increase the risk for nondefect adverse birth outcomes.

Final results from the Betaseron (interferon ß-1b) Pregnancy Registry: a prospective observational study of birth defects and pregnancy-related adverse events.

OBJECTIVE: Women with multiple sclerosis are often diagnosed and treated during their reproductive years. Limited data are available on the safety of treatment during pregnancy. The Betaseron Pregnancy Registry prospectively monitored women exposed to interferon ß-1b (IFNß-1b) during pregnancy to estimate the rates of birth defects, spontaneous abortions (SABs) and other negative outcomes in this population. DESIGN: From 2006 to 2011, this observational registry enrolled women exposed prior to conception or during pregnancy (but prior to or without abnormalities on prenatal screening). Follow-up continued from enrolment through the 4-month paediatric visit. SETTING: Patients in the USA who met these criteria were enrolled in the registry. RESULTS: The registry enrolled 99 pregnant women; 3 were lost to follow-up. The earliest exposure to IFNß-1b occurred during the first trimester for 95 pregnancies and in the third trimester for 1 pregnancy. There were 99 birth outcomes (3 twins), including 86 (86.9%) live births, 11 (11.1%) SABs and 2 (2%) stillbirths. Birth defects were reported in five (5.1%) cases. Rates of birth defects and SAB were not significantly different from population comparators. No developmental concerns were identified at the 4-month paediatric visit. CONCLUSIONS: The small sample size limits the ability to draw definitive conclusions; however, there was no pattern to suggest increased negative outcomes with IFNß-1b. CLINICAL TRIALS REGISTRATION NUMBER: NCT00317564.

Effect of Fertilization and Biopesticides on the Infection of Catharanthus roseus by Phytophthora nicotianae.

Experiments were carried out in a greenhouse to determine the effect of fertilizer concentration (0, 0.5, 1.0, and 2.0× Hoagland solutions) and various commercial biopesticides on the severity of Phytophthora nicotianae infection of Madagascar periwinkle. Application of biopesticides and fertilizer concentration significantly influenced the severity of infection, but there was no significant effect from the interaction of these two factors. Overall, disease severity showed a tendency to increase with the concentration of applied fertilizer. Compared with the control plants, disease was significantly less severe in plants that were treated with the biopesticides, except for plants treated with metabolites of Myrothecium verrucaria (DiTera). However, only the products containing potassium phosphonates and potassium phosphates (FNX-100 and FNX-2500) provided a satisfactory level of control when compared with either the control plants or those that received any of the other products tested. Additional experiments were carried out in growth chambers to test the effects of increasing fertilizer concentrations in plants that were inoculated with different P. nicotianae inoculum levels. In these trials, there was no consistent indication that disease is most severe in plants that received the highest fertilizer concentration even at the highest inoculum level.

Carcinoma in situ and early breast carcinoma survey of the Portuguese Senology Society on treatment in Portugal and its evolution between 1985 and 2000.

By means of a questionnaire sent to Portuguese hospitals which diagnose and treat most female patients with breast cancer, it was intended to assess the situation regarding the treatment of carcinoma in situ and early breast cancer (T1 or T2, N0 or N1), as well as their evolution between 1985 and 2000. The hospital participation rate was 65% and a sample of 865 patients was collected, distributed by the years 1985, 1990, 1995 and 2000. It was observed that, in terms of surgery, there was an increase in conservative surgery, which was over 40% in 2000, as well as an increase in the average of excised axillary lymph nodes. Progress in the surgical approach was similar both in cancer centres and in large and university hospitals, when compared with the other surveyed hospitals. Also, no differences between these two hospital groups in disease-free survival and overall survival were found. Postoperative radiotherapy was employed in more than 90% of the patients submitted to conservative surgery and adjuvant chemotherapy was used in 39% of all the patients, while tamoxifen as adjuvant treatment was used in 58% of the patients.

Carcinoma in situ and early breast carcinoma. Survey of the Portuguese Senology Society on the diagnostic tools used in Portugal and their evolution between 1985 and 2000.

By means of a questionnaire, sent to the Portuguese hospitals which diagnose and treat most female patients with breast cancer, it was intended to assess the situation regarding the diagnosis of carcinoma in situ and early breast cancer (T1 or T2, N0 or N1), as well as their evolution between 1985 and 2000. The hospital participation rate was 65% and a sample of 865 patients was collected, distributed in the years 1985, 1990, 1995 and 2000. It was found that the presentation form of breast cancer in 1985 was of palpable tumour in 87% of the cases, whereas in 2000 this situation only corresponded to 54% of the patients, being most of the remaining patients diagnosed by imaging without palpable tumour. In 94% of the patients, the first diagnostic investigation was mammography, associated or not to echography, and the second most frequent investigation was fine-needle aspiration biopsy. The time evolution of the tumour size showed an increasingly earlier diagnosis. Invasive tumours not more than 1 cm represented 13.2% in 1985 and 20.3% in 2000. On the other hand, breast cancers more than 2 cm and not more than 5 cm decreased from 67.2% in 1985 to 40% in 2000. When oncology centres and some large university hospitals (Group A) were compared to the other hospitals (Group B), there were no significant differences between the diagnostic methods, although the sequence of diagnostic methods was different in the hospitals in Group A versus those in Group B. It was observed that in more differentiated hospitals the diagnosis was achieved increasingly earlier along the studied periods, and this situation did not occur in the other hospitals.

Fulvestrant (Faslodex) versus anastrozole for the second-line treatment of advanced breast cancer in subgroups of postmenopausal women with visceral and non-visceral metastases: combined results from two multicentre trials.

The efficacy of fulvestrant (Faslodex), a novel oestrogen receptor (ER) antagonist that downregulates the ER and has no known agonist effects, was compared with the aromatase inhibitor anastrozole (Arimidex) for the second-line treatment of advanced breast cancer in postmenopausal women with visceral and non-visceral metastases. Assessment was by means of a retrospective subgroup analysis of combined data from two randomised, phase III trials. Objective response (OR) rates were similar in patients treated with fulvestrant and anastrozole, respectively (21.9% versus 19.3%-patients with no visceral metastases; 15.7% versus 13.2%-all of the patients with visceral metastases; 18.8% versus 14.0%-patients with visceral metastases only). The proportion of patients with clinical benefit (CB) was also similar between treatments and between subgroups with and without visceral disease. Fulvestrant is at least as effective as anastrozole, providing a valuable treatment option for advanced breast cancer in postmenopausal women with visceral metastases who have failed on prior endocrine therapy.

Temozolomide in second-line treatment after prior nitrosurea-based chemotherapy in glioblastoma multiforme: experience from a Portuguese institution.

Temozolomide is a new cytotoxic alkylating agent that has recently been approved in Portugal for the treatment of recurrent high-grade glioma. From September 1999 to March 2001, 16 patients with recurrent glioblastoma multiforme who had prior nitrosurea-based chemotherapy [procarbazine, carmustine, vincristine (PCV)] were given temozolomide 150-200 mg/m2/day for 5 days every 28-day cycle. The estimated 1-year survival rate was 16% and the median overall survival was 6.5 months. Despite the small sample size, the overall survival achieved with temozolomide was similar to that of other reports. These promising data suggest that randomized trials should be undertaken to assess its use in first-line therapy its inclusion in combined chemotherapy regimes and its effectiveness with concurrent radiotherapy.

Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment.

PURPOSE: To compare the efficacy and tolerability of fulvestrant (formerly ICI 182,780) and anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. PATIENTS AND METHODS: Patients (n = 451) with advanced breast cancer were randomized to receive fulvestrant 250 mg as a once-monthly (one x 5 mL) intramuscular injection or an oral dose of anastrozole 1 mg in this open, parallel-group, multicenter trial. The primary end point was time to progression (TTP). Secondary end points included objective response (OR) rates, defined as complete response (CR) or partial response (PR), duration of response (DOR), and tolerability. RESULTS: Patients were followed for a median period of 14.4 months. In terms of TTP, fulvestrant was as effective as anastrozole (hazard ratio, 0.98; confidence interval [CI], 0.80 to 1.21; P =.84). Median TTP was 5.5 months for fulvestrant and 5.1 months for anastrozole. OR rates showed a numerical advantage for fulvestrant (20.7%) over anastrozole (15.7%) (odds ratio, 1.38; CI, 0.84 to 2.29; P =.20). Clinical benefit rates (CR + PR + stable disease > or = 24 weeks) were 44.6% for fulvestrant and 45.0% for anastrozole. Median DOR was 14.3 months for fulvestrant and 14.0 months for anastrozole. Both treatments were well tolerated, with 3.2% and 1.3% of fulvestrant- and anastrozole-treated patients, respectively, withdrawn from treatment because of an adverse event. CONCLUSION: Fulvestrant was as effective as anastrozole. These data confirm that fulvestrant is an additional, effective, and well-tolerated treatment for advanced breast cancer in postmenopausal women whose disease progressed on prior endocrine therapy.

Culture of human renal tubular cells: positive selection of kallikrein-containing cells.

Human renal tubular cells derived from nephrectomy specimens were maintained in culture and grown to confluence. Immunocytochemistry, using a panel of antibodies selected for their ability to bind to different cell types within the nephron, showed the cells to be predominantly of epithelial origin with no significant contamination by fibroblasts or cells of endothelial origin. Ten to thirty percent of the cells expressed the putative distal marker, epithelial membrane antigen (EMA), a finding confirmed by flow cytometry. Cells expressing EMA were positively selected from mixed cultures by magnetic activated cell sorting (MACS). Kallikrein activity, expressed as mU/10(6) cells, in the EMA +ve cells, was increased fourfold to sixfold when compared with that in the EMA -ve cells. Cultures of characterized human renal tubular cells and sub-populations enriched with distal cells should prove useful in studies of synthesis and release of parameters of the kallikrein kinin system (KKS) to physiological stimuli. Furthermore, a better understanding of the toxic effect on the KKS of clinically useful drugs, particularly those used for immunosuppression, may lead to therapeutic interventions to lessen unwanted effects.

Urinary kallikrein excretion in normotensive and hypertensive pregnancies: 8 years later.

In a previous longitudinal study of urinary kallikrein (UK) excretion in pregnancy we reported that women with low inactive UK (IUK) to creatinine ratio (IUK:Cr), measured at 16-20 weeks gestation, were at increased risk of developing pregnancy induced hypertension. In this study, 8 years later, we have recalled 14 women who had an IUK:Cr < or = 170 (Gp1) and became hypertensive in late pregnancy and 14 women who had IUK:Cr > 170 and remained normotensive (Gp2). Resting blood pressure (BP) and BP response following application of cutaneous cold to assess vasoconstrictor reactivity were measured. A timed urine sample was also collected for measurements of components of the kallikrein kinin system (KKS): IUK, active UK (AUK), kininogen (UKg), urinary kinins (UKi). Urinary creatinine (UCr) was also measured. The correlation between IUK:Cr during the 1989-1990 study and current measurement was r2 = 0.52, p < 0.0001. Although resting BP was higher in Gp1 than Gp2 this was not significantly different. However, there was a greater change in diastolic BP in Gp1 than in Gp2 in response to the cold pressor test (p < 0.04). Excretion rates of IUK, UKg and UKi were significantly lower in Gp1, p < 0.006, p < 0.003, p < 0.03, respectively. AUK was also reduced in Gp1 but did not reach statistical significance. Women with reduced activity of the renal KKS combined with increased sympathetic drive may be at increased risk of developing hypertension.

Prevention of minor neck injuries in F-16 pilots.

INTRODUCTION: F-16 pilots have a high incidence of minor neck injuries. It was hypothesized that pilots who did neck strengthening exercises and pilots who used other preventive strategies would have fewer injuries. METHOD: We surveyed 268 U.S. Air Force F-16 pilots. Subjects were divided into two groups. Group I, the Early Intervention Group, performed an intervention, or not, from the start of their F-16 careers. Outcomes were measured as a percent of pilots reporting an injury during their F-16 careers. Group II, the Midstream Intervention Group, initiated an intervention after sustaining an injury. Injuries before and after the intervention were compared as a median injury rate per 100 h F-16 time. RESULTS: The 1 -yr prevalence of neck injury was 56.6% and for an F-16 career was 85.4%. For every 100 h in the F-16, the risk of injury increased by 6.9%. Only 26.9% of the pilots routinely did neck strengthening exercises. For the Early Intervention Group, fewer injuries were associated with neck strengthening exercises and placing the head against the seat prior to loading +Gz. For the Midstream Intervention Group, a lower median injury rate was associated with neck strengthening exercises, placing the head against the seat prior to loading, warming up with stretching or isometrics, prepositioning the head prior to loading, and unloading prior to moving the head. Interventions not associated with fewer injuries included body exercises and placing the head against the canopy. CONCLUSION: Certain strategies may prevent neck injuries. Prospective research is needed to confirm these results.

Spatial disorientation in U.S. Army rotary-wing operations.

This paper describes two surveys concerning spatial disorientation (SD) in U.S. Army rotary-wing operations that sought to assess the hazard and to identify recommendations to control it. One survey was of accident records, and the other was of aircrew experiences. Both surveys highlighted the magnitude of the problem. The accident survey showed that 30% of class A to C accidents involved SD as a significant factor, while the aircrew survey showed that 78% of aircrews have been disoriented (8% to the extent that flight safety was threatened). Both surveys showed a significant increase in SD associated with combat operations. Several differences between the two surveys were noted: 90% of the reviewed accidents were thought to involve type I (unrecognized) SD compared with only 43% of the reported incidents; both pilots in a particular aircraft were considered to have been disoriented in at least 59% of accidents compared with 23% of incidents; sudden loss of visual cues ("brownout," "whiteout," or inadvertent entry to instrument meteorological conditions) accounted for 25% of SD accidents compared with 13% of incidents; and 62% of the accidents occurred at night compared with only 36% of incidents. Neither survey showed any association between SD and fatigue or other human factors. The results of both surveys suggested that crew coordination, alerting devices (e.g., audio warnings on the radar altimeter), flight information displays, and autopilot functions would be good targets for improvement.

Modifying effects of amlodipine on cyclosporin A-induced changes in renal function in patients with psoriasis.

OBJECTIVE: To assess the benefit of amlodipine, a calcium channel blocker, on renal function and vasoactive hormones in individuals with normal kidneys and blood pressure and who were being treated with cyclosporin A for refractory psoriasis. DESIGN: An open-label, two-stage, longitudinal study was employed. METHODS: Patients were divided into two groups: Group I received cyclosporin A, 5 mg/kg per day for 6 months titrated down to 2.5-3.5 mg/kg per day for 6 months, then concomitant amlodipine 5 mg/day for 6 months; and Group II received concomitant cyclosporin A, 5 mg/kg per day, and amlodipine, 5 mg/day, for 6 months. Blood pressure, serum creatinine, glomerular filtration rate, urinary magnesium, plasma renin activity and urinary kallikrein excretion were measured before and after treatment. RESULTS: Eighteen patients were enrolled, and 12 completed the study. In Group I (n = 7), 12 months of cyclosporin A therapy significantly increased systolic blood pressure and significantly decreased glomerular filtration rate, plasma renin activity and active urinary kallikrein. Amlodipine reversed these changes. In Group II (n = 5), 6 months of concomitant cyclosporin A and amlodipine significantly reduced active urinary kallikrein levels. No significant changes occurred in the other measured parameters in either group. CONCLUSIONS: Cyclosporin A produces a sustained and significant fall in glomerular filtration rate and urinary kallikrein excretion, even in patients with normal kidneys and blood pressure. Amlodipine is potentially capable of reversing these nephrotoxic effects.

A comparison of the inactive urinary kallikrein:creatinine ratio and the angiotensin sensitivity test for the prediction of pre-eclampsia.

OBJECTIVE: To determine the relation between the inactive urinary kallikrein: creatinine ratio (IUK:Cr) and the angiotensin sensitivity test (AST) at 28 weeks of gestation and to assess each as a screening test for pre-eclampsia. DESIGN: Prospective interventional study. SUBJECTS: Four hundred and fifty-nine normotensive nulliparous women recruited from hospital antenatal clinics. SETTING: John Radcliffe Maternity Hospital, Oxford, and Queen Charlotte's and Chelsea Hospital, London. INTERVENTIONS: A urine sample for IUK:Cr measurement was provided before performing the AST at 28 weeks of gestation. Those women who demonstrated increased sensitivity to angiotensin II were entered into a randomised placebo controlled trial of low dose aspirin for the prevention of pre-eclampsia (CLASP). MAIN OUTCOME MEASURES: The development of pre-eclampsia. RESULTS: The IUK:Cr ratio was significantly lower in those women who showed increased sensitivity to angiotensin II (P < 0.0001 Student's t test). The sensitivity and specificity for detecting pre-eclampsia were, respectively, 22% and 85% for the AST and 67% and 75% for the IUK:Cr. Low-dose aspirin (60 mg) had no effect on the pregnancy outcome. CONCLUSION: There appears to be some relation between the IUK:Cr and AST tests in pregnancy. However, in this population, the IUK:Cr ratio was a better screening test for pre-eclampsia than the AST, but overall neither test was a powerful predictor for the syndrome.

Injury risk for research subjects with spina bifida occulta in a repeated impact study: a case review.

Spina bifida occulta (SBO) occurs in 18-34% of the normal U.S. population. Recently, 16.5% of normal, asymptomatic male soldier volunteer candidates in a U.S. Army Aeromedical Research Laboratory ride motion study were excluded from the study because they had SBO at one vertebral level. Disqualifying this percentage of screened research subject candidates threatened the timely completion of the schedule-intense protocol. Although one study suggests that SBO at spinal level S1 has a higher incidence of posterior disc herniation, the preponderance of clinical literature reports that spina bifida occulta is not a medical problem. The impact literature indicates that lumbosacral vertebral bodies fracture at 7.14 kN in static compression and 20+ G during dynamic vertical impacts. In this paper, we examined the human data observed in ejection seat incidents, the rationale for excluding volunteers with single level SBO and the path of axial load transmission through the lumboscral spine. Based on the findings, we concluded that research volunteers with single level SBO are not at increased risk for injury and recommended inclusion of these volunteers in future studies involving repeated axial impacts due to ride motion.

Adaptive changes in saccade amplitude: oculocentric or orbitocentric mapping?

The saccadic system rapidly adjusts the amplitude of refixation movements to visual targets when abnormal postsaccadic errors occur. This is called rapid saccadic adaptation. It is not yet clear whether this form of adaptation produces changes related to oculocentric mechanisms, such as retinal error or motor error, or orbitocentric mechanisms, such as eye or gaze position. These experiments were designed to test whether rapid saccadic adaptation was orbitocentric, oculocentric, or both by creating a precise sensory motor mismatch between the visual target and the required saccade. Measurements were made to determine adaptive changes as function of (1) saccade direction; (2) eye position; and (3) saccade amplitude. Changes were found to be amplitude- and direction-specific but changes were generalized across a broad range of orbital positions. Two conditions of adaptation: increasing and decreasing amplitude, produced quantitatively similar results, indicating that similar mechanisms underlie both processes. Thus, these data support the view that changes during rapid saccadic adaptation are organized principally in a retina-referenced (oculocentric) map, but only broadly, if at all, in a head-referenced (orbitocentric) map. The changes are consistent with a mechanism represented in a spatial mapping of either retinal or motor error.

Early prediction of pre-eclampsia by measurement of kallikrein and creatinine on a random urine sample.

OBJECTIVE: To assess the measurement of inactive urinary kallikrein (IUK) to creatinine (Cr) ratio (IUK:Cr) on an untimed urine sample, collected between 16 and 20 weeks of pregnancy, as a predictive test for the development of both proteinuric and nonproteinuric pre-eclampsia. DESIGN: A prospective longitudinal study. SETTING: A clinic for antenatal care and a university research department. PARTICIPANTS: Three hundred and seven normotensive women randomly selected (124 nulliparous and 183 parous) attending the antenatal clinic for their booking visit. MAIN OUTCOME MEASURES: 1. Nonproteinuric pre-eclampsia: a rise in diastolic blood pressure of 25 mmHg or more and a crossing of the threshold of 90 mmHg; 2. Proteinuric pre-eclampsia: same as 1. plus the development of significant proteinuria ( > 1 + on urine dipstick). RESULTS: Thirty-seven women developed pre-eclampsia, 12 of whom had proteinuria. Median IUK:Cr ratio in this group was 78.27, compared with 358.19 in the remainder. Analysis of receiver-operator characteristics gave an area under the curve of 0.803. An IUK:Cr ratio of 170 or less in this study predicted nonproteinuric or proteinuric pre-eclampsia with a sensitivity of 70% and a specificity of 86%. Ten of the twelve women who had proteinuria had an IUK:Cr below 170. Median IUK:Cr for those with proteinuric pre-eclampsia was 72.91. CONCLUSIONS: Measurement of IUK:Cr on a urine sample, collected between 16 and 20 weeks of gestation, represents a simple and practical test for the risk of subsequent pre-eclampsia, with a sensitivity and specificity comparable to those reported by other investigators using the widely recognised, but less practical, angiotensin II sensitivity test.

The acute effects of intravenous frusemide on the renal kallikrein kinin system in man: relationship to dose.

Frusemide (f) is a potent natriuretic and diuretic that acts mainly on the luminal side of the ascending loop of Henle (Schlatter et al. (1983) Pflug. Arch. 396: 210-217). F increases the urinary excretion of prostaglandin (PG) E (Mackay et al. (1984) Contr. Nephrol. 41: 160-162) and its diuretic and natriuretic effects are blunted by indomethacin, suggesting that PGs are involved in the cellular action of this drug (Chennavasin et al. (1980) J. Pharmacol. Exp. Ther. 215: 77-81; Waller et al. (1987) Arch. Pharmacodyn. Ther. 290: 145-150). Several investigators have shown a rapid but short-lived rise in urinary kallikrein (UK) excretion after F administration in man, which could represent a 'wash-out' phenomenon rather than indicating a direct involvement of the kallikrein-kinin system (KKS) in mediating the action of F (Zschiedrich et al. (1979) Clin. Sci. 57: 247-250; Waller et al. (1987); Waller et al. (1990) Clin. Sci. 79: 117-121). However, using a mouse model, 5 days treatment with F has been shown to stimulate renal cortical tubular messenger RNA for tissue kallikrein (Penchow and Coghlan (1994) J. Hypertension 12 (Suppl. 3): 887). Urinary excretion of the components of the KKS is believed to reflect the intra-renal activity of the system (Bhoola et al. (1992) Am. Soc. Pharmacol. Exp. Ther. 44: 1-80). Therefore, if the KKS is directly involved in the natriuretic action of F, a dose-related release of the active components of the system would be expected. This study was designed to examine the effect of three intravenous (i.v.) doses of F on the urinary excretion of components of the renal KKS and the relationships of these components with the excretion of water, electrolytes and F.