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Phase II study of cis-diammine(glycolato)platinum, 254-S, in patients with advanced germ-cell testicular cancer, prostatic cancer, and transitional-cell carcinoma of the urinary tract. 254-S Urological Cancer Study Group.

A multicenter cooperative study was conducted to evaluate the clinical efficacy and safety of cis-diammine(glycolato)platinum (254-S), a second-generation anticancer platinum complex, in the treatment of genitourinary cancers. 254-S was given i.v. at 100 mg/m2 at 4-week intervals. As a result, 2 complete responses (CRs) and 8 partial responses (PRs) were obtained in 35 patients with transitional-cell carcinoma (TCC) of the urinary bladder or pyeloureter, 3 PRs were obtained in 16 subjects with prostatic cancer, and 6 CRs and 6 PRs were obtained in 15 patients with testicular cancer, generating objective response rates of 28.6% [95% confidence interval (CI), 14.6%-46.3%], 18.8% (95% CI, 4.0%-45.6%), and 80.0% (95% CI, 51.9%-95.7%), respectively. Bone marrow suppression was the dose-limiting toxicity, although it was reversible. Although no hydration was performed in approx. 40% of the patients, the incidence of nephrotoxic effects was low and most of those encountered were mild, the exception being one patient who showed severe renal insufficiency after the first treatment. Nausea and vomiting occurred in approx. 70% of the patients, but most gastrointestinal toxicities were controlled without antiemetic treatment. In addition, liver-function impairment was rarely observed. We conclude that 254-S is a promising cisplatin analogue for the treatment of genitourinary cancers and is worthy of further investigation in large-scale, randomized comparative studies with other platinum derivatives in both single-agent and combination regimens.

Adult↗

Intra-arterial adriamycin chemotherapy in combination with radiotherapy for advanced bladder cancer.

A total of 38 patients with locally advanced bladder cancer (T2, n = 14; T3, n = 14; T4, n = 10) were treated with intra-arterial Adriamycin chemotherapy in combination with radiotherapy. The clinical as well as the pathological efficacy of this treatment was evaluated in all patients. Clinically, 23 (60.5%) of the 38 patients achieved a complete remission (CR), 12 (31.6%) achieved a partial remission (PR), and 3 (7.9%) remained stable (NC). The pathological efficacy was evaluated according to the criteria of Shimosato et al., with 20 (52.6%) of the 38 patients being categorized as grade IV; 2 (5.3%), as grade III; 12 (31.6%) as grade II; and 4 (10.5%), as grade 0. The 5-year actuarial survival as a function of clinical stage amounted to 91.6% for T2, 50.0% for T3, and 37.4% for T4 (T2 vs T3, P less than 0.05; T2 vs T4, P less than 0.01). The 5-year actuarial survival determined according to the clinical and the pathological efficacy of treatment were 74.1% for CRs, 56.2% for PRs, and 0 for NCs (CR vs NC, P less than 0.01; PR vs NC, P less than 0.01). Surgery for preservation of the bladder was performed in 30 of the 33 patients who achieved clinical and pathological CRs or PRs. The 5-year actuarial survival of these 30 patients was 73.2%. These results demonstrate that this therapy is a useful method for the treatment of locally advanced bladder cancer and that preservation of the bladder might be feasible in patients who achieve clinical and pathological CRs or PRs during this treatment.

Adenocarcinoma↗

Carboplatin activity in untreated metastatic breast cancer patients--results of a phase II study.

Due to the favourable results previously obtained with cisplatin in breast cancer (54% response rate), we studied a second-generation platinum analogue, carboplatin, in patients with previously untreated breast cancer. A total of 20 patients were entered in the study and all were evaluable. The median age was 57 years and all patients were in menopause. Karnofsky scores of 80-100 and 40-70 were registered in 14 and 6 cases, respectively. The predominant metastatic site was soft tissue in 12 subjects, visceral organs in 5 and bone in 3; 14 patients had greater than 2 metastatic sites. Carboplatin was given i.v. at a dose of 400 mg/m2 on day 1, with a 3-week rest period. In 13 patients who did not respond or whose disease recurred after carboplatin treatment, the CMFVP, CAP or FAC regimen was given as second line treatment. Carboplatin activity was observed in 4 patients [2 complete remissions (CRs) and 2 partial responses (PRs)], for a response rate of 20% (4/20); the 2 PRs were observed in soft tissue and bone and the 2 CRs, in lung, liver and bone. Remission lasted 2-10 months (mean, 4 months). CMFVP given as second-line chemotherapy to 13 patients produced 7 PRs (7/13, 54%). Toxicity was moderate, producing no drug-related deaths. Anemia (grade I-II) was recorded in seven patients; grade I-II leukopenia, in six; and grade III-IV leukopenia in two (median leukocyte nadir, 1,600/mm3). Thrombocytopenia was observed in three cases (grades I, II and III; median platelet nadir, 47,800/mm3). Unpleasant nausea/vomiting was pronounced (12 cases of grade III-IV) in 19 subjects. There were no cases of neuro- or nephrotoxicity. Due to permanent myelosuppression, no more than five cycles could be given. Our study showed that, unlike cisplatin, carboplatin given at a dose of 400 mg/m2 has low antitumorigenic activity in breast cancer patients and produces pronounced myelotoxicity. Additional first-line chemotherapy studies using carboplatin are needed to define the antitumorigenic activity of this platinum analogue.

Breast Neoplasms↗

Glial bundles in spinal nerve roots. An immunocytochemical study stressing their nonspecificity in various spinal cord and peripheral nerve diseases.

Glial bundles (GBs) in spinal nerve roots in 86 autopsy cases with various spinal lesions were examined using the peroxidase-antiperoxidase technique for glial fibrillary acidic protein (GFAP). In 19 of 22 cases of Werding-Hoffmann disease (WHD), GBs were present in the anterior roots (ARs) but absent in the youngest age group (age less than 1.5 months at death). GBs were numerous in classical cases (age 3-24 months), accompanying severe damage of the anterior horns and roots, but were less prominent in most cases of protracted course (age 2-8.5 years). Thus, development of GBs in the ARs of motor neuron disease at a young age seems to depend on the clinical type (age at onset and disease duration) and degree of damage to motor neurons and ARs. Varying numbers of GBs were found also in the posterior roots (PRs) of 12 cases of WHD. In 13 patients with amyotrophic lateral sclerosis (ALS), few GBs were observed in the ARs of two and PRs of five cases without apparent relation to other clinicopathologic data. GBs in the PRs of both WHD and ALS might indicate spreading of the degenerative process to sensory neurons despite the absence of pathology detectable by routine histological stains. Numerous GBs were found also in adults affected with polymyelitis in childhood. Varying numbers of GBs were present, however, in many different diseases, such as Friedreich ataxia, Guillain-Barré syndrome, various polyneuropathies, cervical spondylosis, ataxia telangiectasia, metachromatic leukodystrophy, and Leigh syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Treatment of puborectalis syndrome with progressive anal dilation.

PURPOSE: The aim of this study is to assess the ability of progressive anal dilations to improve frequency of spontaneous bowel movements in patients with puborectalis syndrome (PRS). METHOD: Thirteen patients (9 females and 4 males; mean age, 37 years) with severe, chronic constipation caused by PRS were treated with daily, progressive anal dilation for a three-month period. Three dilators of 20, 23, and 27 mm in diameter were used. Dilators were inserted every day for 30 minutes (10 minutes each dilator). Patients were evaluated with anorectal manometry and defecography halfway through treatment, at the end of treatment, and six months after the end of treatment. At six months, patients also underwent physical examination. RESULTS: There was a significant improvement of weekly mean spontaneous bowel movements from zero to six (P < 0.0001), and the need for laxatives decreased from 12 patients with a weekly mean of 4.6 to 2 patients once per week (P < 0.001). Enemas used before treatment by eight patients who had a weekly mean of 2.3 were, after treatment, needed only by three patients once per week (P < 0.01). During straining, tone measured with anorectal manometry decreased from 93 to 62 mmHg after six months of the end of therapy (F = 6.97; P < 0.01), and anorectal angle measured with defecography during the strain increased from 95 degrees to 110 degrees (P = not significant). CONCLUSIONS: Daily progressive anal dilation should be considered as the first and most simple therapeutic approach in patients with PRS.

Adolescent↗

Deleterious effects of inhibition of the renin-angiotensin system in neonatal rats.

The angiotensin I converting enzyme inhibitor (ACEI) perindopril (2 mg/kg body weight), the peripheral vasodilator dihydralazine (DHL) (25 mg/kg body weight) or distilled water was given daily from birth to day 14 to neonatal rats. Blood pressure, plasma creatinine, plasma renin activity (PRA), substrate (PRS) and concentration (PRC) and renin content of kidney tissue sections were evaluated on days 14 and 28. By day 14, a high mortality in the ACEI group was observed. ACEI, but not DHL, led to a significant fall (P < 0.01) in blood pressure, 57 +/- 11 versus 89 +/- 25 in the DHL group and 103 +/- 24 mmHg in controls, and to a dramatic increase in plasma creatinine. PRA and PRS were undetectable in ACEI-treated rats; in contrast, PRC and renal staining with anti-renin antibody were significantly increased in ACEI rats. On day 28, the blood pressure was normal in all groups and plasma creatinine returned to the normal range in ACEI rats. PRA, PRS and PRC were not significantly different in the ACEI group and controls. These results suggest that the renin-angiotensin system (RAS) plays a major postnatal role in the neonatal rat. Inhibition of the RAS during the first 2 weeks of life leads to high mortality, severe hypotension, reversible renal failure and a defect in circulating angiotensinogen.

Aging↗

Postnatal development of the renin-angiotensin system in thyroidectomized rats.

Postnatal changes in plasma renin activity (PRA), plasma renin concentration (PRC), plasma renin substrate (PRS) and plasma angiotensin II concentration (AII) were studied in young thyroidectomized rats from the 4th to the 10th week of life. Although there were no differences in the PRA pattern between thyroidectomized and euthyroid animals, an increase in PRC from the 6th week of life, together with a reduction of the glomerular filtration rate (GFR) and an increase in the fractional excretion of sodium (FENa) from the 8th week of life, was observed in young hypothyroid animals. Moreover, in thyroidectomized animals, PRS and AII declined until the 10th week of age, while in euthyroid animals an increase of PRS and AII was observed between the 8th and 10th weeks of life. These results show that the changes in sodium renal handling following thyroidectomy could have an influence on the RAS components.

Aging↗

Assessing pain and pain relief in geriatric patients with non-pathological fractures with different rating scales.

Although pain is a frequent problem among elderly patients, they are often omitted in clinical trials and few studies have focused on assessing pain relief in this population. The aim of this study was to compare geriatric patients' verbally reported effect of analgesics with changes in pain experience rated with four different rating scales: the Visual Analogue Scale (VAS), the Graphic Rating Scale (GRS), the Numeric Rating Scale (NRS), and the Pain Relief Scale (PRS). Altogether 53 geriatric patients (mean=82 yrs) with non-pathological fractures in 4 geriatric units at a large university hospital were selected. In connection with the administration of analgesics, the patients were asked to "Mark the point that corresponds to your experience of pain just now at rest" on the VAS, GRS and NRS. This was repeated after 1.5-2 hours, and a direct question was asked about whether the analgesic medication given in connection with the initial assessment had had any pain-alleviation effect. Two comparisons were conducted with each patient. The results show that the probability of accomplishing a rating on the VAS, GRS, NRS, and PRS was lower with advancing age in these elderly fracture patients. The correlations between the ratings of the VAS, GRS and NRS were strong and significant (r=0.80-0.95; p<0.001) both at the initial assessments and at the re-assessments. However, the verbally reported effects of the analgesics were often directly opposite to the changes in rated pain. Therefore, application of the VAS, NRS, GRS and PRS for the purpose of assessing pain relief must be combined with supplementary questions that allow the patient to verbally describe possible experience of pain relief.

Aged↗

[The influence of the Tübingen soft palate plate and early cleft closure on swallowing and Eustachian tube function in children with Pierre Robin sequence].

CURRENT KNOWLEDGE: Children with Pierre Robin sequence (PRS) typically have difficulty with bolus transport and swallowing. Due to velopharyngeal insufficiency caused by the cleft palate, a high percentage of the children affected also have impaired Eustachian tube function. AIMS OF THE STUDY: In the literature, substantial information may be obtained on conductive hearing loss in PRS patients; however, no study has yet been performed to investigate whether wearing a soft palate plate and relatively early surgical cleft palate closure positively influence Eustachian tube function. In the present study this question was investigated. METHODS AND RESULTS: A total of 41 PRS children, 27 girls and 14 boys, were included in the study and were examined for hearing ability prior to and after surgical cleft palate closure. All of the children had been wearing a Tübingen soft palate plate until surgical cleft palate closure, which occurred at an age of 3-13 months (mean age 7.3 months). Based on data obtained prior to surgery by BERA, otoacoustic emissions and tympanometry, a hearing loss of more than 30 dB was diagnosed in 68.4% of the children. After 3-6 months, normal hearing ability was found in 70%. CONCLUSIONS: Wearing the Tübingen soft palate plate, and the improved swallowing function resulting from this, as well as early surgical cleft palate closure had a very positive impact on the hearing ability of the children included in the study.

Auditory Threshold↗

Health-related quality of life after laparoscopic and open nephrectomy.

BACKGROUND: Postoperative recovery often is assessed with parameters (pain and return to work) susceptible to bias. This study sought objectively to compare postoperative health-related quality of life (HRQL) after laparoscopic and open nephrectomy with the Postoperative Recovery (PRS) (a validated questionnaire designed to assess pain), activities of daily living (ADL), and HRQL in postoperative patients. METHODS: Patients undergoing contemporaneous laparoscopic and open nephrectomy received the PRS pre- and postoperatively. The results were analyzed with analysis of covariance (ANCOV) and survival analysis. RESULTS: The 33 open nephrectomy and 38 laparoscopic patients in this study were comparable in age, gender, body mass index (BMI) and employment. Laparoscopic operative time was longer (p = 0.015), and the hospital stay was shorter (p<0.001). Laparoscopic patients had higher HRQL scores from postoperative days 3 to 365 (p<0.001), and they returned to preoperative HRQL faster (p<0.001). CONCLUSIONS: An objective HRQL instrument confirms that laparoscopic nephrectomy patients recover faster and with a higher HRQL than open surgery patients. The PRS can be modified for use after other abdominal procedures, and may prove useful for comparisons of other minimally invasive surgical techniques.

Activities of Daily Living↗

Danish version of the Oswestry disability index for patients with low back pain. Part 2: Sensitivity, specificity and clinically significant improvement in two low back pain populations.

In studies evaluating the efficacy of clinical interventions, it is of paramount importance that the functional outcome measures are responsive to clinically relevant change. Knowledge thereof is in fact essential for the choice of instrument in clinical trials and for clinical decision-making. This article endeavours to investigate the sensitivity, specificity and clinically significant improvement (responsiveness) of the Danish version of the Oswestry disability index (ODI) in two back pain populations. Two hundred and thirty three patients with low back pain (LBP) and/or leg pain completed a questionnaire booklet at baseline and 8 weeks follow-up. Half of the patients were seen in the primary (PrS) and half in the secondary sectors (SeS) of the Danish Health Care System. The booklet contained the Danish version of the ODI, along with the Roland Morris Questionnaire, the LBP Rating Scale, the SF36 (physical function and bodily pain scales) and a global pain rating. At follow-up, a 7-point transition question (TQ) of patient perceived change and a numeric rating scale relating to the importance of the change were included. Responsiveness was operationalised using three strategies: change scores, standardised response means (SRM) and receiver operating characteristic (ROC) analyses. All methods revealed acceptable responsiveness of the ODI in the two patient populations which was comparable to the external instruments. SRM of the ODI change scores at 2 months follow-up was 1.0 for PrS patients and 0.3 for SeS (raw and percentage). A minimum clinically important change (MCID) from baseline score was established at 9 points (71%) for PrS patients and 8 points (27%) for SeS patients using ROC analyses. This was dependable on the baseline entry score with the MCID increasing with 5 points for every 10 points increase in the baseline score. We conclude that the Danish version of the ODI has comparable responsiveness to other commonly used functional status measures and is appropriate for use in low back pain patients receiving conservative care in both the primary and secondary sector.

Denmark↗

Intraoral osteotomies using piezosurgery for distraction in an infant with Pierre-Robin sequence.

Airway management in infants with Pierre Robin sequence (PRS) is often challenging. Advancement of the tongue base using mandibular distraction in neonates can avoid tracheotomy and is increasingly propagated. The osteotomies can be performed via intra- and extraoral approaches. Nowadays, for precise bone cutting, piezosurgical devices have been introduced in maxillofacial surgery, which we used for osteotomies via the intraoral approach in the 7-week-old patient presented in this study. Instead of a preoperative CT scan, a 3D data set was generated preoperatively in the operating theatre using a 3D C-arm system. After bilateral transcutaneous pin placement and osteotomies, a second 3D data set was acquired. Primary and secondary reconstructions clearly visualized the patient's bone despite the low level of ossification in newborns and the presence of a large amount of metal implants. In view of the low level of radiation exposure going along with the 3D C-arm imaging, a follow-up examination after removal of the distractors was performed. With this report of a 7-week-old female infant with the diagnosis of PRS, we want to extend the surgical and diagnostic armamentarium for the treatment of infants with PRS.

Electrosurgery↗

Perineal rectosigmoidectomy for rectal prolapse: role of levatorplasty.

BACKGROUND: The management of full thickness rectal prolapse remains controversial. Although abdominal approaches have a lower recurrence rate than do perineal operations, they are associated with a higher morbidity. The aim of this study was to compare the outcomes of perineal rectosigmoidectomy with and without levatorplasty. METHODS: Between 1989 and 1999, a total of 109 consecutive patients (10 men) underwent 120 perineal procedures. These patients were retrospectively evaluated in two groups on the basis of the type of surgery received: perineal rectosigmoidectomy (PRS) or perineal rectosigmoidectomy with levatorplasty (PRSL). Subsequent functional outcome and physiological parameters were assessed. RESULTS: The patients had a mean age of 75.7 years (range, 23.0-94.8 years) and they were followed for an overall mean (in both groups combined) of 28.0 months (range, 0.4-126.4 months) after surgery. Mean duration of surgery was 78.1 min (SD=25.9) and 97.6 min (SD=32.3) in PRS and PRSL, respectively ( p=0.002, unpaired t test). There was no significant difference between the two groups in terms of hospital stay, morbidity or mortality. Recurrence rates and mean time interval to recurrence were, respectively, 20.6% and 45.5 months in PRS compared to 7.7% and 13.3 months in PRSL ( p=0.049, chi-square test; p=0.001, unpaired t test). Both groups had significant improvements in postoperative incontinence score ( p<0.0001, Wilcoxon's matched-pairs signed-ranks test), however, there were no significant changes in anorectal manometric findings and pudendal nerve terminal motor latency assessment. CONCLUSIONS: Perineal rectosigmoidectomy with levatorplasty is associated with a lower recurrence rate and a longer time to recurrence than perineal rectosigmoidectomy alone. Levatorplasty should be offered to patients when a perineal approach for rectal prolapse is selected.

Adult↗

Phase I/II study of amrubicin, a novel 9-aminoanthracycline, in patients with advanced non-small-cell lung cancer.

PURPOSE: Amrubicin is a novel, totally synthetic 9-aminoanthracycline. The present phase I/II study was performed to define its maximum-tolerated dose (MTD), efficacy and toxicity in the treatment of previously untreated patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemonaive patients were required to have cytologically or histologically proven measurable NSCLC, an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2, and adequate organ functions. Amrubicin was administered by daily intravenous injection for 3 consecutive days every 3 weeks. RESULTS: In a phase I study, four patients were enrolled at dose level 1 (40 mg/m(2)/day) and four at dose level 2 (45 mg/m(2)/day). No dose limiting toxicity (DLT), which was defined as toxicity consisting of grade 4 neutropenia and leukopenia lasting four days or more, and grade 3 or 4 toxicity other than neutropenia, leukopenia, anorexia, nausea/vomiting, and alopecia, was observed at these dose levels. Subsequently, at dose level 3 (50 mg/m(2)/day), 3 of 5 patients experienced DLTs (leukopenia, neutropenia, thrombocytopenia, or gastrointestinal complications). The MTD and recommended dose (RD) were determined to be 50 mg/m(2)/day and 45 mg/m(2)/day, respectively. Three partial responses (PRs) were achieved in 13 patients (response rate, 23.1%) in a phase I study. In a phase II study, 15 patients were assessable for efficacy and toxicity at the RD, and four PRs were obtained (response rate, 26.7%). The major toxicities were leukopenia and neutropenia, while non-hematologic toxicities were mild. The overall response rate in the combined patient population of the phase I/II study was 25.0% (7 PRs in 28 patients), with a 95% confidence interval of 10.7% to 44.9%. CONCLUSION: Amrubicin exerted promising antitumor activity on NSCLC with acceptable toxicity.

Adult↗

Pathogenesis of hypertension in Cushing's syndrome.

Steroid production, plasma renin activity (PRA) and plasma renin substrate (PRS) were measured in eight patients with hypertension due to Cushing's syndrome of benign origin. Despite elevation of cortisol secretion in all patients, hypokalemia and suppressed PRA was noted in the one subject with a functioning adrenal adenoma. PRA was normal in six patients on an unrestricted sodium intake but was markedly increased in the two patients on low salt diets. PRS was significantly increased during active disease, but decreased substantially with treatment. The absence of uniform hypokalemia and of suppression of renin indicates that mineralocorticoid production could not account for the increase in arterial pressure. It is suggested that glucocorticoid-induced hypertension may be initiated by alterations in vascular responsiveness to pressor agents and that elevated PRS levels may contribute to increase angiotensin formation.

17-Ketosteroids↗

Electrical activation of visual pathways substitutes for tonic light input in triggering EEG correlates of food reward during conditioned behavior in cats.

Cats trained to press a lever for 1 cc of milk reward normally show during the consummatory response high voltage 6--8 c/sec EEG synchronization associated with epicortical positive steady potential shift over the primary and secondary visual projections. The emergence of this postreinforcement synchronization (PRS) and Reward Contingent Positive Variation (RCPV) is known to depend upon appropriate gustatory input and presence of ambient light, although visual perception of reward and/or environment is not essential as shown in cats wearing translucent "milky" contact lenses. Training the animals in a paradigm in which a "light-off" cue signaled the availability of reward, and thus assigned positively reinforcing quality to the dark condition, also failed to restore the PRS-RCPV phenomenon in the absence of light. However, brief electrical stimuli applied to either the optic tract or the lateral geniculate nucleus substituted for unpatterned light input and fully restored the PRS-RCPV in the dark. The suprathreshold stimuli were effective only during the consummatory response. Maximum effect could be produced during a brief time period between 0.8 and 1.5 sec after the onset of consummatory response as judged by lapping activity, thus showing the specificity of the effect of visual input. Even during a relaxed wakefulness after satiation or during slow wave sleep or REM sleep the same electric stimuli were ineffective although they produced well-developed evoked potentials with all characteristic wave components. The results indicate that brain pathways utilize unpatterned i.e. noisy visual input in complex integrative processes involving gustatory input.

Animals↗

The neurosteroid 3 alpha, 5 apha-THP has antiseizure and possible neuroprotective effects in an animal model of epilepsy.

Some anticonvulsant drugs may suppress seizures by enhancing activity of GABAergic systems. Progesterone (P)'s anti-convulsant and neuroprotective effects may be due to the steroid's actions on GABAA-benzodiazepine receptor complexes (GBRs) rather than intracellular progestin receptors (PRs), as many P metabolites have a greater effect in vitro on benzodiazepine binding and Cl-flux than P, but poor affinity for PRs. If P's actions are due to metabolism to a progestin more potent at GBRs, then systemic administration of one of those P metabolites should also prevent CNS damage. To test this hypothesis male rats were implanted with a bipolar electrode, aimed above the perforant pathway. Experimental animals received the 5 alpha-reduced P metabolite most effective at GBRs, 5 alpha-pregnan-3 alpha-ol-20-one (3 alpha,5 alpha-THP) 2.5 mg/kg s.c., 3 h prior to perforant pathway stimulation, while control animals received sesame oil vehicle. The duration of chewing and drooling and the incidence of wet dog shakes, partial and full seizures were reduced during perforant pathway stimulation in animals pre-treated with 3 alpha,5 alpha-THP compared to vehicle. Two weeks later, animals pre-treated with 3 alpha,5 alpha-THP had shorter latencies and distances to find a hidden platform in a Morris Water maze task. 3 alpha,5 alpha-THP pre-treatment also reduced damage to CA1 and CA3 layers of the hippocampus and preserved the number of neurons in the hilar region. These data indicate that the neurosteroid metabolite of P, 3 alpha,5 alpha-THP, can have anticonvulsant and may have neuroprotective effects in an animal model of epilepsy. Further, these data suggest that the mechanism of P's protective and anticonvulsant effects may be via GBRs rather than PRs.

Animals↗

Simultaneous measurement of renin and renin substrate concentration in human plasma by a simple kinetic method.

A simple kinetic method is described for measurement of plasma renin concentration (PRC) and plasma renin substrate concentration (PRS) in human plasma. It is based on the radioimmunological determination of angiotensin I generated when a plasma sample is incubated at 37 degrees C for 2, 4, 6 and 8 h. The use of exogenous renin and renin substrate preparations are not required. The specific velocity constant of reaction (K) was used to deduce the PRC. PRS determination was based on the stoichiometric conversion of renin substrate to angiotensin I. PRC and PRS have been determined in plasma from healthy subjects, plasma from health subjects 3 h after oral furosemide administration and in plasma from women, 12-20 weeks normally pregnant.

Angiotensin II↗