Phyto- and Bio-Chemical evaluation of Diospyros kaki L. cultivated in Egypt and its biological activities / Avaliação fito e bioquímica de Diospyros kaki L. cultivado no Egito e suas atividades biológicas

Abstract Diospyros kaki L. or Costata cultivar is the main persimmon variety progressively consumed in the Egyptian market and exportation. The objective of this study was to investigate the bioprotective effects of the alcoholic extract of fruits as well as leaves of D. kaki using in-vivo rat models. Petroleum ether extracts of fruits and leaves were analytically characterized for saponifiable and unsaponifiable compounds by GC/MS. Main flavonoids were chromatographically isolated from 80% aqueous methanol extract of leaves. Chemical evaluation for fruits and leaves namely, content of moisture, ash, proteins, fatty acids, amino acids, fat and water soluble vitamins, minerals, carotenoids was carried out. Total antioxidant activity was determined by radical scavenging effects using DPPH assay. The effect on biochemical parameters and its biological activity were also performed. Results revealed the identification of the major compounds of saponifiable and unsaponifiable matters of fruits and leaves. Scopoletin, as well as, kaempferol, luteolin, rutin and apigenin 7-O-glucoside were isolated and identified. It showed that this plant can provide a good nutritional value and it is safe regarding the kidney and liver functions, good source that help in enhancing the antioxidant defense against free radicals. No abnormal effects were found in lipids profile on experimental animals and there were good results in the ratio of HDL and LDL cholesterol. Also, this plant can help in optimizing blood sugar, enhancing the level of blood haemoglobin. It is concluded that D. kaki displays a good source of nutrients and bioactive compounds that may contribute to its therapeutic benefits against the risk of disease complications.

Resumo Diospyros kaki L. ou Costata é a principal variedade de caqui progressivamente consumida no mercado e exportação egípcia. O objetivo deste estudo foi investigar os efeitos bioprotetores do extrato alcoólico de frutos e folhas de D. kaki utilizando modelos de ratos "in vivo". Extratos de éter de petróleo provenientes de frutos e folhas foram caracterizados analiticamente para compostos saponificáveis ​​e insaponificáveis ​​por GC/MS. Os principais flavonoides foram isolados cromatograficamente, a partir de 80% de extrato aquoso de folhas de metanol. Foi realizada avaliação química de frutos e folhas, ou seja, de teor de umidade, cinzas, proteínas, ácidos graxos, aminoácidos, vitaminas lipossolúveis e solúveis em água, minerais, carotenoides. Foi caracterizada a atividade antioxidante, utilizando ensaio (DPPH). O efeito nos parâmetros bioquímicos e sua atividade biológica também foram analisados. Os resultados revelaram a identificação dos principais compostos saponificáveis e insaponificáveis de frutos e folhas. Escopoletina, bem como kaempferol, luteolina, rutina e apigenina 7-O-glicosídeo foram isolados e identificados. Também demonstraram que esta planta pode proporcionar um bom valor nutricional e é segura em relação às funções renais e hepáticas, boa fonte que ajuda a melhorar a defesa antioxidante contra os radicais livres. Não foram encontrados efeitos anormais no perfil lipídico em testes em animais, e houve um efeito satisfatório na relação de colesterol HDL e LDL. Além disso, esta planta pode ajudar na otimização do açúcar no sangue, aumentando o nível de hemoglobina. Conclui-se que o D. kaki apresenta uma boa fonte de nutrientes e de compostos bioativos que contribuem para seus benefícios terapêuticos e contra o risco de complicações de doenças.

Phyto- and Bio-Chemical evaluation of Diospyros kaki L. cultivated in Egypt and its biological activities.

Diospyros kaki L. or Costata cultivar is the main persimmon variety progressively consumed in the Egyptian market and exportation. The objective of this study was to investigate the bioprotective effects of the alcoholic extract of fruits as well as leaves of D. kaki using in-vivo rat models. Petroleum ether extracts of fruits and leaves were analytically characterized for saponifiable and unsaponifiable compounds by GC/MS. Main flavonoids were chromatographically isolated from 80% aqueous methanol extract of leaves. Chemical evaluation for fruits and leaves namely, content of moisture, ash, proteins, fatty acids, amino acids, fat and water soluble vitamins, minerals, carotenoids was carried out. Total antioxidant activity was determined by radical scavenging effects using DPPH assay. The effect on biochemical parameters and its biological activity were also performed. Results revealed the identification of the major compounds of saponifiable and unsaponifiable matters of fruits and leaves. Scopoletin, as well as, kaempferol, luteolin, rutin and apigenin 7-O-glucoside were isolated and identified. It showed that this plant can provide a good nutritional value and it is safe regarding the kidney and liver functions, good source that help in enhancing the antioxidant defense against free radicals. No abnormal effects were found in lipids profile on experimental animals and there were good results in the ratio of HDL and LDL cholesterol. Also, this plant can help in optimizing blood sugar, enhancing the level of blood haemoglobin. It is concluded that D. kaki displays a good source of nutrients and bioactive compounds that may contribute to its therapeutic benefits against the risk of disease complications.

Eastern Canadian Gastrointestinal Cancer Consensus Conference 2018.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference was held in Halifax, Nova Scotia, 20-22 September 2018. Experts in radiation oncology, medical oncology, surgical oncology, and pathology who are involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics in the management of pancreatic cancer, pancreatic neuroendocrine tumours, hepatocellular cancer, and rectal and colon cancer, including ■ surgical management of pancreatic adenocarcinoma,■ adjuvant and metastatic systemic therapy options in pancreatic adenocarcinoma,■ the role of radiotherapy in the management of pancreatic adenocarcinoma,■ systemic therapy in pancreatic neuroendocrine tumours,■ updates in systemic therapy for patients with advanced hepatocellular carcinoma,■ optimum duration of adjuvant systemic therapy for colorectal cancer, and■ sequence of therapy in oligometastatic colorectal cancer.

Phyto- and Bio-Chemical evaluation of Diospyros kaki L. cultivated in Egypt and its biological activities

Abstract Diospyros kaki L. or Costata cultivar is the main persimmon variety progressively consumed in the Egyptian market and exportation. The objective of this study was to investigate the bioprotective effects of the alcoholic extract of fruits as well as leaves of D. kaki using in-vivo rat models. Petroleum ether extracts of fruits and leaves were analytically characterized for saponifiable and unsaponifiable compounds by GC/MS. Main flavonoids were chromatographically isolated from 80% aqueous methanol extract of leaves. Chemical evaluation for fruits and leaves namely, content of moisture, ash, proteins, fatty acids, amino acids, fat and water soluble vitamins, minerals, carotenoids was carried out. Total antioxidant activity was determined by radical scavenging effects using DPPH assay. The effect on biochemical parameters and its biological activity were also performed. Results revealed the identification of the major compounds of saponifiable and unsaponifiable matters of fruits and leaves. Scopoletin, as well as, kaempferol, luteolin, rutin and apigenin 7-O-glucoside were isolated and identified. It showed that this plant can provide a good nutritional value and it is safe regarding the kidney and liver functions, good source that help in enhancing the antioxidant defense against free radicals. No abnormal effects were found in lipids profile on experimental animals and there were good results in the ratio of HDL and LDL cholesterol. Also, this plant can help in optimizing blood sugar, enhancing the level of blood haemoglobin. It is concluded that D. kaki displays a good source of nutrients and bioactive compounds that may contribute to its therapeutic benefits against the risk of disease complications.

Resumo Diospyros kaki L. ou Costata é a principal variedade de caqui progressivamente consumida no mercado e exportação egípcia. O objetivo deste estudo foi investigar os efeitos bioprotetores do extrato alcoólico de frutos e folhas de D. kaki utilizando modelos de ratos in vivo. Extratos de éter de petróleo provenientes de frutos e folhas foram caracterizados analiticamente para compostos saponificáveis e insaponificáveis por GC/MS. Os principais flavonoides foram isolados cromatograficamente, a partir de 80% de extrato aquoso de folhas de metanol. Foi realizada avaliação química de frutos e folhas, ou seja, de teor de umidade, cinzas, proteínas, ácidos graxos, aminoácidos, vitaminas lipossolúveis e solúveis em água, minerais, carotenoides. Foi caracterizada a atividade antioxidante, utilizando ensaio (DPPH). O efeito nos parâmetros bioquímicos e sua atividade biológica também foram analisados. Os resultados revelaram a identificação dos principais compostos saponificáveis e insaponificáveis de frutos e folhas. Escopoletina, bem como kaempferol, luteolina, rutina e apigenina 7-O-glicosídeo foram isolados e identificados. Também demonstraram que esta planta pode proporcionar um bom valor nutricional e é segura em relação às funções renais e hepáticas, boa fonte que ajuda a melhorar a defesa antioxidante contra os radicais livres. Não foram encontrados efeitos anormais no perfil lipídico em testes em animais, e houve um efeito satisfatório na relação de colesterol HDL e LDL. Além disso, esta planta pode ajudar na otimização do açúcar no sangue, aumentando o nível de hemoglobina. Conclui-se que o D. kaki apresenta uma boa fonte de nutrientes e de compostos bioativos que contribuem para seus benefícios terapêuticos e contra o risco de complicações de doenças.

A systematic review of MR imaging as a tool for evaluating haemophilic arthropathy in children.

Our purposes were to determine: (i) whether there is direct evidence that currently available MRI techniques are accurate for early diagnosis of pathological findings in haemophilic arthropathy; (ii) whether there is an MRI scoring system that best correlates with clinical/radiological constructs for evaluation of haemophilic arthropathy; (iii) whether there is an MRI scoring system that best correlates with clinical/radiological constructs for evaluation of haemophilic arthropathy. Articles were screened using MEDLINE (n = 566), EMBASE (n = 201), and the Cochrane Library (n = 1). Two independent reviewers assessed articles for inclusion under the overarching purposes of the review by using the Standards for Reporting of Diagnostic Accuracy (STARD) tool, and the quality of the studies were graded using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. The electronic literature search retrieved 777 references (after duplicates were removed). A total of 32 studies were chosen for inclusion from the results of the search and review of bibliographical references. Using the STARD tool, seven studies were of excellent quality of reporting, and using the QUADAS-2 tool, 10 studies were judged to be of adequate quality. There is 'fair' evidence to recommend MRI as an accurate test for detecting evidence of haemophilic arthropathy and the use of second or third generation MRI scales for assessing haemophilic arthropathy. However, there is no evidence that screening of early intra-articular soft tissue bleed with MRI improves the functional status of joints over time.

Interstitial fluid glucose dynamics during insulin-induced hypoglycaemia.

AIMS/HYPOTHESIS: Glucose sensors often measure s.c. interstitial fluid (ISF) glucose rather than blood or plasma glucose. Putative differences between plasma and ISF glucose include a protracted delay during the recovery from hypoglycaemia and an increased gradient during hyperinsulinaemia. These have often been investigated using sensor systems that have delays due to signal smoothing, or require long equilibration times. The aim of the present study was to define these relationships during hypoglycaemia in a well-equilibrated system with no smoothing. METHODS: Hypoglycaemia was induced by i.v. insulin infusion (360 pmol.m(-2).min(-1)) in ten non-diabetic subjects. Glucose was sequentially clamped at approximately 5, 4.2 and 3.1 mmol/l and allowed to return to normoglycaemia. Subjects wore two s.c. glucose sensors (Medtronic MiniMed, Northridge, CA, USA) that had been inserted for more than 12 h. A two-compartment model was used to quantify the delay and gradient. RESULTS: The delay during the fall in plasma glucose was not different from the delay during recovery (8.3+/-0.67 vs 6.3+/-1.1 min; p=0.27) and no differences were observed in the ratio of sensor current to plasma glucose at basal insulin (2.7+/-0.25 nA.mmol(-1).l) compared with any of the hyperinsulinaemic clamp phases (2.8+/-0.18, 2.7+/-0.021, 2.9+/-0.21; p=NS). The ratio was significantly elevated following recovery to normoglycaemia (3.1+/-0.2 nA.mmol(-1).l; p<0.001). CONCLUSIONS/INTERPRETATION: The elevated ratio suggests that the plasma to ISF glucose gradient was decreased following hypoglycaemia, possibly due to increased skin blood flow. Recovery from hypoglycaemia is not accompanied by a protracted delay and insulin does not increase the plasma to s.c. ISF glucose gradient.

Relation of left ventricular dilation during acute myocardial infarction to systolic performance, diastolic dysfunction, infarct size and location.

The quantification of left ventricular (LV) volumes and assessment of their relation to systolic and diastolic dysfunction, infarct size and anatomic location were performed in 54 patients with a first acute myocardial infarction (AMI). Blood pool radionuclide angiography was used to assess LV end-diastolic, end-systolic, and stroke volume indexes, ejection fraction and peak diastolic filling rate. Infarct size was estimated from plasma MB creatine kinase activity. Substantial LV dilation occurred within the initial 24 hours of AMI. The peak diastolic filling rate was low, even in those patients with a normal ejection fraction. In comparison with inferior AMI (n = 25), patients with anterior AMI (n = 29) had a larger end-diastolic volume index (105 +/- 8 vs 81 +/- 4 ml/m2, p less than 0.01) and end-systolic volume index (64 +/- 7 vs 37 +/- 4 ml/m2, p less than 0.001), but similar stroke volume index (41 +/- 3 vs 43 +/- 2 ml/m2, difference not significant). No significant relation was noted between infarct size estimated by MB creatine kinase and any volumetric index. On repeat study (day 10 after AMI), end-diastolic and end-systolic volume indexes increased further (p less than 0.05 vs day 1) but ejection fraction and peak diastolic filling rate were unchanged. It was concluded that: (1) LV dilation occurs within hours of AMI in both inferior and anterior AMI, but is more marked in the latter; (2) significant LV diastolic dysfunction is the rule, even in patients with preserved LV systolic function; and (3) LV dilation is an early compensatory mechanism that maintains normal stroke volume, even in patients with severely reduced LV function.

Retroperitoneal perforation of the rectum during barium enema examination.

Colorectal perforation during barium enema examination is rare. The authors report the case of an 84-year-old woman in whom retroperitoneal perforation of the rectum occurred during barium enema examination. Potential mechanisms of injury include trauma, overinflation of the balloon, recent instrumentation and associated disease of the rectal mucosa. When the colon has been well prepared before examination, and air alone, not barium, has been insufflated into the retroperitoneum, then such injuries may be managed successfully without operation, as in this case.

Dissociation between global and regional systolic and diastolic ventricular function during coronary occlusion and reperfusion.

Indexes of global ventricular function such as the ejection fraction (EF) and the peak diastolic filling rate (PDFR) are often used to assess the effects of coronary recanalization in patients with myocardial infarction. In this investigation we assessed the relationship between these global indexes and directly measured indexes of regional function during 15 minutes of coronary occlusion followed by 120 minutes of reperfusion in 22 open-chest dogs. A computerized nuclear cardiac probe was used to assess EF and PDFR. Indexes of regional function were measured by Doppler ultrasonic wall-thickening probes. During coronary occlusion, paradoxical systolic thinning occurred and the EF and PDFR decreased an average of 31.6% and 24.4%, respectively. During reperfusion the EF and PDFR improved rapidly and at 60 minutes were similar to baseline. Systolic wall thickening improved more gradually and remained abnormal throughout reperfusion. Likewise, indexes of diastolic function (mean rate to half end-diastolic thinning and late diastolic thinning fraction) recovered slowly and remained abnormal throughout reperfusion (78% and 69.7%, respectively). The correlation between the rate of change of global and regional function was poor during both coronary occlusion and reperfusion. Thus, during coronary occlusion the global and regional indexes of ventricular function undergo directionally similar changes. However, during coronary reperfusion the global indexes do not reflect the slow recovery of the stunned myocardium.

Comparison of left ventricular diastolic function as determined by nuclear cardiac probe, radionuclide angiography, and contrast cineangiography.

In this investigation, determinations of peak diastolic filling rate (PDFR) and ejection fraction (EF) by two distinct nuclear techniques--gated radionuclide angiography (RNA) and nuclear cardiac probe (NCP)--were compared with contrast ventriculography in 44 patients with coronary artery disease (CAD). In addition, PDFR was tested as a potential index of the severity of disease. Good agreement in PDFR was found between NCP and contrast ventriculography (r = 0.83, p less than 0.001), but there was poor correlation between RNA and contrast ventriculography. Ejection fraction measured by either RNA or NCP correlated well with contrast ventriculography (r = 0.96 and r = 0.73, respectively). A positive correlation was found between PDFR and the EF measured by the NCP (r = 0.79) and by contrast ventriculography (r = 0.64), but poor correlation was found between these parameters by RNA. Patients with multivessel CAD had lower PDFR than patients with single vessel disease when studied by the NCP (1.6 +/- 0.4 versus 2.5 versus 0.6 EDV/sec [mean +/- s.d.], p less than 0.0001), but not by RNA. Thus, compared with contrast ventriculography, determination of PDFR is more accurate by NCP than by RNA. Furthermore, the PDFR measured by NCP, but not by RNA, may be a potentially useful index of the extent of CAD.

Quantitative analysis of thallium-201 uptake and washout before and after transluminal coronary angioplasty.

Transluminal coronary angioplasty has become an important therapeutic modality in the treatment of coronary artery disease. The effects of coronary angioplasty on regional myocardial perfusion have been reported in only a small series of patients, employing subjective analysis of thallium-201 perfusion scintigrams. Thus, we studied 61 patients with quantitative analysis of thallium-201 uptake and washout before and after undergoing angioplasty. Prior to angioplasty, there were 105 areas in 47 patients with abnormal thallium-201 uptake during exercise, with a mean uptake of 49 +/- 1.3%. The uptake of thallium-201 in these same areas increased to 71.3 +/- 1.9% post angioplasty (P less than 0.0001), and 68 (65%) of the areas showing abnormal uptake returned to normal. Abnormalities in washout of thallium-201 before angioplasty were seen more frequently than in uptake (150 vs 105 areas, P less than 0.05), with 8 patients having abnormal washout in the presence of totally normal uptake. Thallium-201 washout in the abnormal areas improved from 16 +/- 2.8 pre angioplasty to -23 +/- 1.8% post angioplasty (P less than 0.001). Normalization resulted in 6 of the 8 patients with exclusively washout abnormality. Residual abnormalities in uptake and/or washout were seen in 53% of the patients, usually in areas with prior myocardial infarction or supplied by a vessel with significant stenosis which did not undergo angioplasty. Improved thallium-201 uptake and washout corresponded to reductions in percent coronary area stenosis (89 +/- 1.0 to 36 +/- 2.0%, P less than 0.001) and transstenotic pressure gradient (42 +/- 3.0 to 9.0 +/- 2.0 mm Hg, P less than 0.001). Thus, quantitative analysis of thallium-201 uptake and washout provided objective evidence for improved myocardial perfusion after coronary angioplasty. Due to a fairly high prevalence of residual perfusion abnormalities after this procedure, optimal assessment of benefits requires quantitative comparison of thallium uptake and washout before and after coronary angioplasty.

Safety profile of aztreonam in clinical trials.

The clinical safety of aztreonam in the treatment of suspected aerobic gram-negative infections was assessed in 346 patients who received single doses and in 2,388 patients who received multiple doses. Of those administered multiple doses, 163 (6.8%) experienced 172 adverse clinical effects. The most common were local reactions at the injection site, rash, diarrhea, and nausea and/or vomiting. Among aztreonam and control groups, three-fold increases in serum aspartate aminotransferase (SGOT) and serum alanine aminotransferase (SGPT) values occurred at comparably low frequencies; the mean values of SGOT and SGPT were slightly higher in patients administered aztreonam than in those given cefamandole. Treatment with aztreonam was discontinued in 51 (2.1%) of 2,388 patients because of adverse clinical effects or abnormal laboratory test values. Suprainfections (infections due to new pathogens occurring at the original site of infection during treatment with the study drug that were treated with another antibiotic) were reported in 2%-6% of aztreonam-treated patients, a frequency similar to that observed in control groups. Aztreonam is well tolerated and has a safety profile similar to that of other beta-lactam antibiotics.

Crossover comparison of captopril and propranolol as step 2 agents in hypertension.

The efficacy of captopril treatment was compared with that of propranolol in a single-blind crossover study in 14 patients with essential hypertension uncontrolled on diuretic alone. Both captopril (37.5 to 75 mg daily) and propranolol (60 to 120 mg daily), in combination with hydrochlorothiazide (50 mg daily), caused a significant fall in sitting systolic and diastolic blood pressure. Heart rate, plasma renin activity, and plasma aldosterone data were consistent with the effects of converting enzyme inhibition or beta blockade. Both drugs were well tolerated. Captopril appeared to be equivalent in efficacy and safety to propranolol when added to hydrochlorothiazide. It may be considered as an alternative step 2 antihypertensive agent, especially in patients experiencing unwanted effects on beta blockers.

Captopril in hypertension; seven years later.

Captopril was first administered to hypertensive patients 7 years ago. The relatively high dosage employed and the severity of diseases in the patient population initially led to a high frequency of side effects. Subsequently, an increase in the time intervals for dose titration and the earlier addition of a diuretic have made it possible to reduce the daily dose, thus significantly improving the drug's safety profile without compromising its antihypertensive effect. In a worldwide postmarketing surveillance study of captopril, 6,737 hypertensive patients were enrolled, of whom 3,219 were treated for at least 1 year. Patients had a mean entry blood pressure of 183 (+/- 31)/111 (+/- 16) mm Hg while still receiving an average of 2.3 antihypertensive drugs. However, 10.3% were not receiving therapy before entering the study. 1,811 patients (29% of those for whom relevant data were available) had impaired renal function on entry (serum creatinine concentration greater than or equal to 1.6 mg/dl). The hypertension of 881 of the patients (13.1%) was classified as mild to moderate. By design, the types of patients, dosage schedules, and patient monitoring requirements were consistent with the recommendations of the manufacturer at the time the study was initiated. The results of the study showed that long-term antihypertensive efficacy was maintained with a mean captopril dose of approximately 150 mg/day, when used either as monotherapy or more frequently with a diuretic. This dosage was associated with satisfactory control of blood pressure and a considerable reduction in the 12 months' cumulative frequency of drug discontinuation because of adverse reactions (5.8%).(ABSTRACT TRUNCATED AT 250 WORDS)

Juglone concentration in soil beneath black walnut interplanted with nitrogen-fixing species.

Juglone concentration was measured in soils collected under a 14-year-old black walnut (Juglans nigra L.) plantation containing plots of pure walnut and of walnut mixed with either autumn-olive (Elaeagnus umbellata Thunb.) or European black alder (Alnus glutinosa (L.) Gaertn.). Juglone concentrations declined with soil depth and distance from the walnut tree. Concentrations in autumn-olive-walnut plots were statistically lower than concentrations in European black alder-walnut or pure walnut plots. The concentration of juglone in soil in European black alder-walnut plots was apparently sufficient to cause the onset of black alder mortality.

Long-term antihypertensive therapy with captopril.

Most forms of hypertension require life-long treatment; thus, it is important to determine the continuing effectiveness and safety of any new therapeutic agent. While participating in various investigational studies, 7103 hypertensive patients received captopril, of whom 4397 were treated for 3 months to 4 years. The 4-year patients included 2498 with mild or moderate essential hypertension (diastolic pressure less than 120 mm Hg), 893 with severe essential hypertension, and 517 with renovascular hypertension. Repeated examinations of these long-term therapy patients, the majority of whom also were receiving a diuretic, indicated no drug tolerance to the combination, i.e., there was continuing control of the blood pressure without significant increases in dosage or addition of other drugs. Side-effects occurring during the first few months of captopril administration (rash, taste disturbances, and, rarely, neutropenia) were not a problem during prolonged therapy. A few patients (70/7,103, or 1.0%) developed proteinuria, usually reversible and seldom associated with any deterioration of renal function. The proteinuria occurred most often in patients who had preexisting renal disease and were receiving high doses of the drug. There were no significant changes in key biochemical parameters. A total of 230 patients discontinued treatment for failure to maintain adequate blood pressure reduction, and 397 for side-effects. The estimated 4-year cumulative frequency of drug discontinuance for side-effects was 11.6% (life table method), which compares favorably with other classes of antihypertensive drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Tympanic membrane retraction and middle-ear pressure.

MHA assessment and LR observation are poor indicators of MEP. Clinical assessment of the MHA in normal living ears, within the range 30 degrees to 75 degrees, correlates poorly with MEP measured by impedance tympanometry, within the range of -300 to +160 mm H2O. Variation of MEP in fresh temporal bones demonstrated that MHA, LR and postero-superior segment retraction remained unchanged between -50 and -400 mm H2O and between +50 and +400 mm H2O. The change in position of the TM over the range +50 to -50 mm H2O corresponded to the maximum compliance change on the tympanogram i.e. the width of the tympanometric notch.

Long-term treatment of essential hypertension with Nadolol and Hydrochlorothiazide: a two-year follow-up.

After 3 weeks of placebo administration, thirty-two mildly or moderately hypertensive patients were treated with hydrochlorothiazide (HCZ) for 3 weeks, then with HCZ plus nadolol, a new beta-adrenergic blocker, for 2 years. The dose of HCZ was 50 mg once daily for all except two patients, who received 50 mg twice a day. The dose of nadolol ranged from 40 mg to 240 mg, once daily. The average supine blood pressure decreased from 182/110 mm Hg at the end of the placebo period to 170/104 mm Hg at the end of treatment with HCZ alone. Nadolol was added to the regimen, and the average supine blood pressure decreased further to 132/88 mm Hg at the end of 3 months of combined therapy. It remained essentially unchanged for the duration of the 2-year study, and no increases in the dosage of either drug were needed. Side-effects were mild, and none required a change in dosage. A once-daily dose of nadolol combined with HCZ appears to be safe and effective therapy for the long-term treatment of mild or moderate essential hypertension.