Insight into Automatic Image Diagnosis of Ear Conditions Based on Optimized Deep Learning Approach.

Examining otoscopic images for ear diseases is necessary when the clinical diagnosis of ear diseases extracted from the knowledge of otolaryngologists is limited. Improved diagnosis approaches based on otoscopic image processing are urgently needed. Recently, convolutional neural networks (CNNs) have been carried out for medical diagnosis to obtain higher accuracy than standard machine learning algorithms and specialists' expertise. Therefore, the proposed approach involves using the Bayesian hyperparameter optimization with the CNN architecture for automatic diagnosis of ear imagery database including four classes: normal, myringosclerosis, earwax plug, and chronic otitis media (COM). The suggested approach was trained using 616 otoscopic images, and the performance of this approach was assessed using 264 testing images. In this paper, the performance of ear disease classification was compared in terms of accuracy, sensitivity, specificity, and positive predictive value (PPV). The results produced a classification accuracy of 98.10%, a sensitivity of 98.11%, a specificity of 99.36%, and a PPV of 98.10%. Finally, the suggested approach demonstrates how to locate optimal CNN hyperparameters for accurate diagnosis of ear diseases while taking time into account. As a result, the usefulness and dependability of the suggested approach will lead to the establishment of an automated tool for better categorization and prediction of different ear diseases.

Mitigation of salinity stress effects on kochia (Bassia scoparia L.) biomass productivity using biochar application.

Salinity continues to be a key factor limiting food security and agricultural sustainability in arid and semi-arid countries. Biochar has been promoted to reduce the risk of saline irrigation. In a controlled study, physiological and morphological growth factors of kochia plants that were irrigated with tap water (S1) and saline water (S2) were assessed to identify the ameliorative effects of biochar amendment to the soil at different levels (B1: 0%, B2: 2%, B3: 5%, and B4: 10%. According to our findings, salinity stress negatively affected morphological and physiological growth parameters of kochia plants by decreasing the fresh and dry weight (25% and 28%, respectively), plant height (30%), circumference (46%), total chlorophyll (51%), and relative water content (29%) when compared to the controls. Furthermore, electrolyte leakage increased considerably (19%) due to salt stress. Significant morphological and physiological growth enhancements were seen at all biochar levels in comparison to the control treatment, with the highest level increasing plant height by 55%, circumference by 76%, total chlorophyll concentrations by 121%, and relative water content by 28%. Furthermore, it resulted in a 36% reduction in the stressed plants' electrolyte leakage. The findings demonstrated biochar's benefits in reducing salinity's negative effects on kochia plants.

• This study provides new data about the specifying the impact of using biochar on salinity concentration and the growth parameters of kochia plants. This investigation demonstrated a significant results in terms of that the salinity stress relative to using biochar.• Biochar is crucial for stimulating and activating biochemical defensive mechanisms against salt stress; yet, research in this area is lacking.• Biochar has shown that it is crucial to stimulate biochemical defense mechanisms against salinity stress• It was found that using biochar as a soil supplement improved morphological, physiological, and biochemical characteristics of the kochia plant by increasing fresh and dried weight per plant, plant height, plant circumference, chlorophyll concentrations, and relative water content while lowering electrolyte leakage in stressed kochia plants. This research will aid in increasing kochia's early development and stand establishment in saline circumstances.

Water Poverty Index: a Tool for Water Resources Management in Jordan.

In terms of water resources, Jordan is considered one of the poorest countries in the world. Water resources management is one of the available options to decrease the gap between demand and resources. Water resources management requires optimum use of the available water resources taking into consideration resources availability, resources reliability, water use pattern, in addition to the socioeconomic issues. One of the most important aspects is human behaviour which has a strong impact on water management and on the ecosystem. Therefore, there is a need to follow a sustainable approach to improve the management and the understanding of the difficulties of water issues by integrating the physical, social, economic, and environmental aspects, as well as linking water issues to poverty indicator. In this paper, Water Poverty Index (WPI) will be used as a tool for water resources management. WPI was calculated based on five parameters: resources, access to water, capacity, use, and the environment. The Jordanian water strategy targets will be used to forecast the water situation in 2025 and calculate WPI. In 2002, the WPI was calculated and found at 46.3%, in comparison with higher figures for other countries. WPI was calculated for the year 2018, and the results showed a value of 50.7%. If the national water strategy targets and improvements will be successfully implemented, by 2025, the value is expected to be increased to 56.38%. Water resources are the most sensitive component of WPI. COVID-19 increased the rate of unemployment and poverty ratio which will affect WPI negatively. It's concluded that WPI could be used as a valuable indicator to help evaluate the running plans and monitor the management performance.

Classification of Ear Imagery Database using Bayesian Optimization based on CNN-LSTM Architecture.

The external and middle ear conditions are diagnosed using a digital otoscope. The clinical diagnosis of ear conditions is suffered from restricted accuracy due to the increased dependency on otolaryngologist expertise, patient complaint, blurring of the otoscopic images, and complexity of lesions definition. There is a high requirement for improved diagnosis algorithms based on otoscopic image processing. This paper presented an ear diagnosis approach based on a convolutional neural network (CNN) as feature extraction and long short-term memory (LSTM) as a classifier algorithm. However, the suggested LSTM model accuracy may be decreased by the omission of a hyperparameter tuning process. Therefore, Bayesian optimization is used for selecting the hyperparameters to improve the results of the LSTM network to obtain a good classification. This study is based on an ear imagery database that consists of four categories: normal, myringosclerosis, earwax plug, and chronic otitis media (COM). This study used 880 otoscopic images divided into 792 training images and 88 testing images to evaluate the approach performance. In this paper, the evaluation metrics of ear condition classification are based on a percentage of accuracy, sensitivity, specificity, and positive predictive value (PPV). The findings yielded a classification accuracy of 100%, a sensitivity of 100%, a specificity of 100%, and a PPV of 100% for the testing database. Finally, the proposed approach shows how to find the best hyperparameters concerning the Bayesian optimization for reliable diagnosis of ear conditions under the consideration of LSTM architecture. This approach demonstrates that CNN-LSTM has higher performance and lower training time than CNN, which has not been used in previous studies for classifying ear diseases. Consequently, the usefulness and reliability of the proposed approach will create an automatic tool for improving the classification and prediction of various ear pathologies.

Phylogenomic analysis of SARS-CoV-2 from third wave clusters in Malaysia reveals dominant local lineage B.1.524 and persistent spike mutation A701V.

The emergence of a third wave of COVID-19 infection in Malaysia since September 2020 has led to imminent changes in public health prevention and control measures. As high as 96.2% of registered COVID-19 cases and 88.5% of confirmed deaths in Malaysia occurred during this third wave of infection. A phylogenomic study on 258 SARS-CoV-2 full genomes from February 2020-February 2021 has led to the discovery of a novel Malaysian lineage B.1.524. This lineage contains another spike mutation A701V that co-exists with the D614G spike mutation that was predominant in most of the third-wave clusters. The study provides vital genomic insights on the rapid spread of the SARS-CoV-2 variants in Malaysia in conjunction with the presence of a dominant SARS-CoV-2 lineage during the third wave of COVID-19 infection.

A 3D image segmentation for lung cancer using V.Net architecture based deep convolutional networks.

Lung segmentation of chest CT scan is utilised to identify lung cancer and this step is also critical in other diagnostic pathways. Therefore, powerful algorithms to accomplish this accurate segmentation task are highly needed in the medical imaging domain, where the tumours are required to be segmented with the lung parenchyma. Also, the lung parenchyma needs to be detached from the tumour regions that are often confused with the lung tissue. Recently, lung semantic segmentation is more suitable to allocate each pixel in the image to a predefined class based on fully convolutional networks (FCNs). In this paper, CT cancer scans from the Task06_Lung database were applied to FCN that was inspired by V.Net architecture for efficiently selecting a region of interest (ROI) using the 3D segmentation. This lung database is segregated into 64 training images and 32 testing images. The proposed system is generalised by three steps including data preprocessing, data augmentation and neural network based on the V-Net model. Then, it was evaluated by dice score coefficient (DSC) to calculate the ratio of the segmented image and the ground truth image. This proposed system outperformed other previous schemes for 3D lung segmentation with an average DCS of 80% for ROI and 98% for surrounding lung tissues. Moreover, this system demonstrated that 3D views of lung tumours in CT images precisely carried tumour estimation and robust lung segmentation.

Phylogenomic analysis of SARS-CoV-2 from third wave clusters in Malaysia reveals dominant local lineage B.1.524 and persistent spike mutation A701V

@#The emergence of a third wave of COVID-19 infection in Malaysia since September 2020 has led to imminent changes in public health prevention and control measures. As high as 96.2% of registered COVID-19 cases and 88.5% of confirmed deaths in Malaysia occurred during this third wave of infection. A phylogenomic study on 258 SARS-CoV-2 full genomes from February 2020-February 2021 has led to the discovery of a novel Malaysian lineage B.1.524. This lineage contains another spike mutation A701V that co-exists with the D614G spike mutation that was predominant in most of the third-wave clusters. The study provides vital genomic insights on the rapid spread of the SARS-CoV-2 variants in Malaysia in conjunction with the presence of a dominant SARS-CoV-2 lineage during the third wave of COVID-19 infection.

Soybean isoflavone affects in rabbits: Effects on metabolism, antioxidant capacity, hormonal balance and reproductive performance.

Though soybean isoflavones (SBI) have pharmaceutical properties, the compounds also have endocrine disrupting activities that may adversely affect fertility of mammals. The effects of SBI on metabolism, antioxidant capacity, hormonal balance and reproductive performance of male rabbits were investigated. Adult male rabbits (n = 21) fed an isoflavone-free diet were orally treated with 0 (control; CON), 5 (small; LSBI) or 20 (large; HSBI) mg of SBI/kg body weight/day for 12 weeks. Both SBI doses resulted in lesser blood plasma total protein concentrations, while there were no effects on glucose and cholesterol concentrations compared to CON. The HSBI-treated males had the greatest (P < 0.05) blood plasma total antioxidant capacity and least malondialdehyde. Treatment with both SBI doses induced a 43% increase in triiodothyronine concentrations (P < 0.05) and 82% in reaction times (P < 0.001), while decreased sperm concentrations (P = 0.01) and blood plasma testosterone concentrations (P = 0.017) 26% and 19%, respectively. The total functional sperm fraction was less (P < 0.05) in the HSBI group; however, there was no effect of the LSBI treatment as compared to values for the CON group. The kindling rates of females mated to HSBI-treated males tended to be less (P = 0.081) than those of does mated with LSBI or CON males. In conclusion, only the HSBI treatment improved antioxidant status; whereas, treatment with both LSBI and HSBI doses induced a hormonal imbalance which led to an impaired testis function indicating the sensitivity of the adult male reproductive system to SBI actions.

Prolonged exposure of dietary phytoestrogens on semen characteristics and reproductive performance of rabbit bucks.

The effects of inclusion of different sources of dietary phytoestrogens on antioxidant capacity, hormonal balance, libido, semen quality, and fertility of rabbit bucks were studied. Twenty-one, adult, fertile, V-line bucks were randomly allocated into 3 homogenous groups (n = 7/treatment) and received control diet (phytoestrogens-free diet, CON) or soybean meal isoflavones-containing diet (SMI) or linseed meal lignans-containing diet (LML) for 12 wk. The diets were formulated to be isocaloric and isonitrogenous. The concentrations of isoflavones in the SMI diet were 24.04 mg/100 g dry matter (DM) daidzein and 13.10 mg/100 g DM genistein. The major phytoestrogen detected in the LML diet was secoisolariciresinol (36.80 mg/100 g DM). Treatment had no effects on body weight, feed intake and rectal temperature of bucks. Compared with control, bucks fed the SMI and LML diets had higher (P < 0.001) blood plasma total antioxidant capacity (0.98 ± 0.12, 1.50 ± 0.13, and 2.29 ± 0.17 mM/L for CON, SMI, and LML, respectively), and lower (P < 0.01) blood plasma malondialdehyde (2.76 ± 0.23, 1.76 ± 0.16, and 1.70 ± 0.18 nmol/mL for CON, SMI, and LML, respectively), whereas activities of reduced glutathione and superoxide dismutase (SOD) enzymes were not affected. Bucks fed the SMI and LML diets had greater (P < 0.001) concentrations of blood plasma triiodothyronine. Feeding the SMI and LML diets decreased (P < 0.01) libido (8.26 ± 0.71, 12.18 ± 0.97, and 14.12 ± 1.12 s for CON, SMI, and LML, respectively), sperm concentration (327.7 ± 21.6, 265.8 ± 36.8, and 226.5 ± 20.1 × 106/mL for CON, SMI, and LML, respectively), testosterone (5.16 ± 0.95, 3.91 ± 0.63, and 3.04 ± 0.92 ng/mL for CON, SMI, and LML, respectively), and seminal plasma fructose compared with the CON diet. The percentage of progressive motile sperm was improved (P < 0.001) by both phytoestrogen-containing diets. Feeding the SMI diet increased (P = 0.02) the percentage of live sperm compared with CON, whereas LML resulted in an intermediate value. Dietary treatment of bucks did not affect kindling rates or litter sizes of does, and did not affect birth weights or viabilities of kits. In conclusion, prolonged consumption of dietary isoflavones or lignans did not impair semen fertilizability. This may be due to the benefits of antioxidant activity or due to the benefits of other components in the diet. Dietary phytoestrogens did evoke obvious decreases in libido and steroidogenesis with altered semen parameters.

Semen quality, testosterone, seminal plasma biochemical and antioxidant profiles of rabbit bucks fed diets supplemented with different concentrations of soybean lecithin.

A total of 28 adult V-line rabbits were fed ad libitum a control diet or a diet supplemented with 0.5%, 1.0% and 1.5% soybean lecithin (SL) for 12 weeks. Bucks that received 0.5%, 1.0% or 1.5% dietary SL had a higher ejaculate volume, mass motility, sperm concentration, total sperm output and total motile sperm. Dietary SL reduced the percentage of dead sperm and increased the normal sperm, and this concurred with an increase in blood testosterone concentration. Blood and seminal plasma total lipid, acid phosphatase and seminal plasma alkaline phosphatase were significantly increased because of inclusion of SL. Interestingly, SL reduced blood and seminal plasma thiobarbituric acid-reactive substances while increasing blood and seminal plasma glutathione content, glutathione S-transferase, glutathione peroxidase and superoxide dismutase activity. Conception rate and litter size at birth and weaning were also significantly improved. Practically, it could be suggested that SL is a suitable supplement for improving semen quality, antioxidant status, reproductive traits and the economic efficiency of V-line rabbit bucks and 1% is an adequate concentration.

An acute infusion of lactic acid lowers the concentration of potassium in arterial plasma by inducing a shift of potassium into cells of the liver in fed rats.

BACKGROUND: Potassium (K(+)) input occurs after meals or during ischemic exercise and is accompanied by a high concentration of L-lactate in plasma (P(L-lactate)). METHODS: We examined whether infusing 100 µmol L-lactic acid/min for 15 min would lead to a fall in the arterial plasma K(+) concentration (P(K)). We also aimed to evaluate the mechanisms involved in normal rats compared with rats with acute hyperkalemia caused by a shift of K(+) from cells or a positive K(+) balance. RESULTS: There was a significant fall in P(K) in normal rats (0.25 mM) and a larger fall in P(K) in both models of acute hyperkalemia (0.6 mM) when the P(L-lactate) rose. The arterial P(K) increased by 0.8 mM (p < 0.05) 7 min after stopping this infusion despite a 2-fold rise in the concentration of insulin in arterial plasma (P(Insulin)). There was a significant uptake of K(+) by the liver, but not by skeletal muscle. In rats pretreated with somatostatin, P(Insulin) was low and infusing L-lactic acid failed to lower the P(K). CONCLUSIONS: A rise in the P(L-lactate) in portal venous blood led to a fall in the P(K) and insulin was permissive. Absorption of glucose by the Na(+)-linked glucose transporter permits enterocytes to produce enough ADP to augment aerobic glycolysis, raising the P(L-lactate) in the portal vein to prevent postprandial hyperkalemia.

Occult risk factor for the development of cerebral edema in children with diabetic ketoacidosis: possible role for stomach emptying.

The incidence of cerebral edema during therapy of diabetic ketoacidosis (DKA) in children remains unacceptably high-this suggests that current treatment may not be ideal and that important risk factors for the development of cerebral edema have not been recognized. We suggest that there are two major sources for an occult generation of osmole-free water in these patients: first, fluid with a low concentration of electrolytes that was retained in the lumen of the stomach when the patient arrived in hospital; second, infusion of glucose in water at a time when this solution can be converted into water with little glucose. In a retrospective chart review of 30 patients who were admitted with a diagnosis of DKA and a blood sugar > 900 mg/dL (50 mmol/L), there were clues to suggest that some of the retained fluid in the stomach was absorbed. To minimize the likelihood of creating a dangerous degree of cerebral edema in patients with DKA, it is important to define the likely composition of fluid retained in the stomach on admission, to look for signs of absorption of some of this fluid during therapy, and to be especially vigilant once fat-derived brain fuels have disappeared, because this is the time when glucose oxidation in the brain should increase markedly, generating osmole-free water.

Antenatal Bartter's syndrome: why is this not a lethal condition?

There are four themes in this teaching exercise for Professor McCance. The first challenge was to explain how a premature infant with Bartter's syndrome could survive despite having such a severe degree of renal salt wasting. Second, the medical team wanted to know why there was such a dramatic decrease in the natriuresis in response to therapy, despite the presence of a permanent molecular defect that affected the loop of Henle. Third, Professor McCance was asked why this patient seemed to have a second rare disease, AQP2 deficiency type of nephrogenic diabetes insipidus. The fourth challenge was to develop a diagnostic test to help the parents of this baby titrate the dose of indomethacin to ensure an effective dose while minimizing the likelihood of developing nephrotoxicity. The missing links in this interesting story emerge during a discussion between the medical team and its mentor.

Uncovering the basis of a severe degree of acidemia in a patient with diabetic ketoacidosis.

In this teaching exercise, the goal is to demonstrate how an application of principles of physiology can reveal the basis for a severe degree of acidaemia (pH 6.81, bicarbonate <3 mmol/l (P(HCO(3))), PCO(2) 8 mmHg), why it was tolerated for a long period of time, and the issues for its therapy in an 8-year-old female with diabetic ketoacidosis. The relatively low value for the anion gap in plasma (19 mEq/l) suggested that its cause was both a direct and an indirect loss of NaHCO(3). Professor McCance suggested that ileus due to hypokalaemia might cause this direct loss of NaHCO(3), and that an excessive excretion of ketoacid anions without NH(4)(+) in the urine accounted for the indirect loss of NaHCO(3). In addition, he suspected that another factor also contributing to the severity of the acidaemia was a low input of alkali. He was also able to explain why there was a 16-h delay before there was a rise in the P(HCO(3)) once therapy began. The missing links in this interesting story, including a possible basis for the hypokalaemia, emerge during the discussion between the medical team and Professor McCance.

Quantitative structure-property relationship study of retention time of some pesticides in gas chromatography.

A quantitative structure-property relationship (QSPR) study based on multiple linear regression (MLR) and artificial neural network (ANN) techniques is carried out to investigate the retention time behavior of some pesticides on the DB-5ms fused-silica column in gas chromatography. Five descriptors selected in the MLR model are: first component WHIM index (E1v), highest eigenvalue n.7 of burden matrix / weighted by atomic van der waals volume (BEHv7); average connectivity index Chi-2 (X2a), 3D-MoRSE signal 23 weighted by atomic Sanderson electronegativity (MoR23m); and principal moments of inertia B (PMIB). A 5-5-1 ANN is also generated to investigate the retention behavior of described pesticides using the same descriptors MLR model as inputs. The statistical parameters derived from MLR and ANN for all molecules are: correlation coefficient (R)(MLR) = 0.929, standard errors (SE)(MLR) = 3.452, R(ANN) = 0.943, and SE(ANN) = 3.112. The mean of relative errors between the MLR and ANN calculated and the experimental values of the retention times for the prediction set are 13.8% and 9.04%, respectively. The correlation coefficient and standard error of ANN model compared with MLR models showed the superiority of ANNs over regression models. This is partly due to the fact that ANN considers the interaction between different parameters as well as nonlinear relation.

A hyperglycaemic hyperosmolar state in a young child: diagnostic insights from a quantitative analysis.

This teaching exercise demonstrates how the application of principles of physiology can identify the cause of a severe degree of hyperglycaemia (plasma glucose concentration 80 mmol/l) in a very young patient with newly diagnosed diabetes mellitus, determine whether the patient has diabetic ketoacidosis, and highlight the potential risks for this patient on admission and during initial therapy. A consultation with Professor McCance was sought to determine whether this patient had an unusual degree of 'insulin resistance'. There were also uncertainties regarding the acid-base diagnosis. The patient did not appear to have an important degree of metabolic acidosis as judged from his pH of 7.39 and plasma bicarbonate concentration of 20 mmol/l in arterial blood; hence the diagnostic impression was that he had a hyperglycaemic hyperosmolar state. However, his plasma anion gap was significantly elevated, and remained so for 60 h, despite the administration of insulin. Issues in management concerning the basis for this severe degree of hyperglycaemia and how to minimize the risk of developing cerebral oedema are addressed. The missing links in this interesting story emerge during a discussion between the medical team and their mentor, Professor McCance.

Estrogen and progesterone receptors and telomerase enzyme immunohistochemical detection in gestational trophoblastic tumors.

The purpose of this study is to evaluate the immunohistochemical detection of telomerase enzyme and estrogen receptor (ER) and progesterone receptor (PGR) in gestational trophoblastic neoplasia (GTN) and its clinical significance. Formalin-fixed paraffin blocks for 30 patients (24 with molar pregnancy, 3 with choriocarcinoma, and 3 with placental site trophoblastic tumor) as cases and six products of conception samples from patients with incomplete abortion as controls were included in the study. Immunohistochemical detection of the telomerase catalytic protein and ER and PGR was carried out using streptavidin-biotin-peroxidase method. All control tissues were negative for telomerase and ER expression, while five of six were PGR positive. Significant positive telomerase expression was detected in all gestational trophoblastic tumors (three of six partial moles, 12 of 18 complete moles, three of three choriocarcinomas, and two of three placental site trophoblastic tumors). Nine of 24 molar pregnancies were followed by GTN. Molar pregnancies followed by GTN were associated with higher serum beta-hCG (human chorionic gonadotrophic hormone), larger uterine size for gestational age, negative ER expression, negative PGR expression, and positive telomerase expression. All patients with molar pregnancy with negative telomerase expression (9 of 24) showed spontaneous regression after evacuation. Positive telomerase expression and its immunohistochemical detection are associated with the development of GTN. Negative telomerase expression is highly predictive of postmolar spontaneous regression. Patients with molar pregnancies with negative telomerase expression can be saved the long-term follow-up. ER and PGR expression do not show a significantly different pattern in molar tissues, while negative expression is associated with developing GTN. Cautions on the use of postmolar hormonal contraception may be unjustified.

The patient with a severe degree of metabolic acidosis: a deductive analysis.

This teaching exercise demonstrates how principles of physiology might help in identifying the cause of a particularly severe case of metabolic acidosis and making appropriate decisions about therapy. The patient's plasma pH was 7.00 and their plasma bicarbonate concentration was 2 mmol/l. Because the time course of the patient's illness was believed to be <24 h, this suggested that a large quantity of acid had been added to the body in this short time period, but the medical team managing the case could not identify any acid that could have been produced rapidly by endogenous processes, or was ingested by the patient. Moreover, there was a question about how such a very low arterial PCO(2) (8 mmHg) could be sustained. Even once the diagnosis was made, there were issues to resolve concerning therapy. These included questions about how much sodium bicarbonate to administer, and what dangers might arise during this therapy. The missing links in this interesting story emerge during a discussion between the medical team and their imaginary mentor, Professor McCance.

An improved approach to the patient with metabolic acidosis: a need for four amendments.

Clinicians should identify life-threatening issues in patients with metabolic acidosis. These threats may be present before therapy begins and/or anticipated after therapy commences. By adding four amendments, short-comings in the commonly used clinical approaches for the diagnosis of metabolic acidosis can be overcome. First, a definition of metabolic acidosis should consider not only the concentration of bicarbonate but also the content of bicarbonate in the extra cellular fluid compartment. The latter requires a quantitative estimate of the ECF volume, which can be obtained using the hematocrit and/or the total protein concentration in plasma. Second, to determine if the basis for metabolic acidosis was the addition of acids or the loss of NaHCO 3 , one must hunt for new anions, not only in plasma, but also in the urine. Third, it is important to measure the venous as well as the arterial PCO2 to assess the capacity to buffer H+ while minimizing H + binding to intracellular proteins. Fourth, to assess the role of the kidney in a patient with metabolic acidosis, the urine osmolal gap and the concentration of creatinine in the urine should be measured to provide an estimate of the rate of excretion of ammonium.

Recurrent uric acid stones.

A 46-year-old female had a history of recurrent uric acid stone formation, but the reason why uric acid precipitated in her urine was not obvious, because the rate of urate excretion was not high, urine volume was not low, and the pH in her 24-h urine was not low enough. In his discussion of the case, Professor McCance provided new insights into the pathophysiology of uric acid stone formation. He illustrated that measuring the pH in a 24-h urine might obscure the fact that the urine pH was low enough to cause uric acid to precipitate during most of the day. Because he found a low rate of excretion of NH(4)(+) relative to that of sulphate anions, as well as a high rate of citrate excretion, he speculated that the low urine pH would be due to a more alkaline pH in proximal convoluted tubule cells. He went on to suspect that there was a problem in our understanding of the function of renal medullary NH(3) shunt pathway, and he suggested that its major function might be to ensure a urine pH close to 6.0 throughout the day, to minimize the likelihood of forming uric acid kidney stones.