Clinical efficacy of various root canal obturating methods in primary teeth: a comparative study.

AIM: The purpose of this in vivo study was to evaluate and compare the efficacy of different obturating methods used in primary teeth, when obturated using a combination of zinc oxide and iodoform paste (Endoflas F.S.). MATERIALS AND METHODS: A group of 29 patients aged 3-9 years and a total of 64 teeth were selected. These 64 teeth (32 anterior teeth=32 canals, and 32 posterior teeth=80 canals) were randomly divided into 4 groups. Teeth were obturated with Lentulo spiral, pressure syringe, bi-directional spiral and Pastinject. Post-operative evaluation was done for: quality of canal obturation, (underfilled, optimally filled, overfilled) and presence of voids. RESULTS: Pastinject exhibited the highest number of optimally filled canals, while the highest number of underfilled canals were observed with bi-directional spiral, and the highest number of overfilled canals were observed with pressure syringe. A minimum number of voids was present in canals filled with the Pastinject technique and pressure syringe. CONCLUSION: These results suggest that Pastinject was the most effective technique for obturation of primary teeth.

Relationship of leukocyte CR1 transcript and protein with the pathophysiology and prognosis of systemic lupus erythematosus: a follow-up study.

Complement Receptor 1 (CR1) is a key complement regulatory protein (CRP) involved in the clearance of immune complexes. Earlier, we reported a marked decline of leukocyte CR1 (L-CR1) transcript and protein in patients with active systemic lupus erythematosus (SLE) and suggested L-CR1 transcript as a putative non-invasive disease marker for SLE. This follow-up study involving 18 patients with active SLE was conducted for further confirmation of the relationship between L-CR1 and SLE. Blood samples from the patients were collected on day 1 of the diagnosis (0 month) and at different time intervals (3 and 6 months) for analysis of L-CR1 transcript and L-CR1 protein by semi-quantitative reverse-transcriptase-polymerase chain reaction (RT-PCR) and western blotting respectively. Within 6 months, 15 patients entered remission. On day 1, the mean values of L-CR1 transcript (8.42 ± 3.53) and L-CR1 protein (4683 ± 1094) in the SLE patients were 6 times and 12 times lower than the normal controls (n = 103). At the end of month 6, these values increased by 4.5 and 6.5 times respectively for CR1 transcript (37.86 ± 8.52) and protein (30,265 ± 8614). Simultaneously, the SLE Disease Activity Index (SLEDAI) scores decreased by 4.8 times (4.47 ± 3.32) as compared with the scores obtained on day 1 (21.45 ± 5.67). Moreover, CR1 values correlated negatively with the SLEDAI scores. Levels of L-CR1 protein and transcript remained low in the three patients who did not enter remission. All of the above results suggested that an increase in the levels of L-CR1 related to good prognosis. Since the levels of L-CR1 protein is influenced by variables like proteolytic cleavage and secretion from leukocytes, the values of L-CR1 transcript on day 1 and subsequent follow-up points may bring a better insight into the state of the disease activity. An extended follow-up study is needed to confirm the significance of L-CR1 as a prognostic marker for SLE.

Prospective Nonrandomized Comparison Between Open and Robot-Assisted Kidney Transplantation: Analysis of Midterm Functional Outcomes.

Introduction: To compare short- and midterm outcomes of the first 55 patients undergoing robot-assisted kidney transplant (RAKT) with patients undergoing open kidney transplant (OKT) during the same period in a tertiary care hospital. Materials and Methods: Data of all end-stage renal disease patients undergoing renal transplant were prospectively maintained. All graft kidneys were harvested laparoscopically. Both RAKT and OKT were performed using standardized techniques, and all RAKTs were performed by a single experienced robotic surgeon. Chi-square test/Fisher exact test was done for categorical data, and Mann-Whitney U test was done for continuous data. Discrete variables were expressed in absolute numbers and percentages. For all tests, p < 0.05 was considered significant. All results were expressed as mean ± standard deviation or median with range. Results: Between April 2016 and September 2018, 55 patients underwent RAKT. The same was compared with 152 patients who underwent OKT. The two groups were comparable in terms of age, gender, and body mass index. Duration on hemodialysis was significantly higher in the RAKT group, and hemoglobin and donor kidney glomerular filtration rate was significantly better in the RAKT group. Requirement of perioperative analgesia was significantly less in the RAKT group. Rewarm ischemia time was significantly longer in the RAKT group. The fall in serum creatinine was slower in RAKT group till 3 months. The serum creatinine levels were statistically similar in the two cohorts at 3 months (p = 0.082), which was maintained at median 29 months of follow-up (p = 0.067). Tacrolimus levels on postoperative day 2 were found to be significantly higher in RAKT cohort (17.98 ± 14.41) vs OKT cohort (11.38 ± 6.93). Surgical-site infections were rare in the RAKT group. Conclusions: RAKT confers advantage of decreased wound morbidity with similar functional outcomes compared with OKT in midterm. It looks promising; however, long-term follow-up of larger numbers of patients is needed.

Adrenocortical Suppression in Children with Nephrotic Syndrome Treated with Low-Dose Alternate Day Corticosteroids.

Corticosteroids form the mainstay of therapy for all forms of nephrotic syndrome. The long-term use of this medication is associated with serious side effects including adrenocortical suppression. The primary objective of this study was to identify adrenocortical suppression (assessed by single morning serum cortisol levels) in children with nephrotic syndrome on treatment with low-dose alternate day steroids. This cross-sectional study was conducted in the Department of Pediatrics in a tertiary care hospital from January 2014 to January 2015. Seventy children (1-18 years) with nephrotic syndrome (steroid sensitive and resistant) who were in remission and on low-dose alternate day steroids for at least 8 weeks or had received steroids of 2 mg/kg/d for at least 2 weeks in the last 1 year (infrequent relapsers) were enrolled. Relevant history was taken, clinical examination was done and blood samples were drawn for serum cortisol, lipid profile, kidney function tests, fasting blood sugar, glycated hemoglobin (HbA1c), and serum albumin. Forty percent (28/70) children had adrenocortical suppression as assessed by low morning serum cortisol levels. The mean serum cortisol levels were 188 nmol/L and were significantly lower in frequently relapsing individuals (85.9 nmol/L) as compared to other types of nephrotic syndrome (P = 0.05). The prevalence of adrenocortical suppression was higher in steroid-resistant patients (57%) as compared to 28% in frequently relapsing and 11% in steroid-dependent patients. Fifty-seven percent of patients with adrenocortical suppression had short stature while 50% had obesity. All individuals had normal serum HbA1c levels. The cumulative steroid doses and total duration of corticosteroid therapy were significantly higher in patients with adrenocortical suppression. Children with nephrotic syndrome treated with low-dose alternate day steroids have a high prevalence of adrenocortical suppression on screening with single morning cortisol sample. Those with frequently relapsing or steroid-resistant diseases are at a higher risk of suppression.

Enhancement of coral calcification via the interplay of nickel and urease.

Corals are the main reef builders through the formation of calcium carbonate skeletons. In recent decades, coral calcification has however been impacted by many global (climate change) and local stressors (such as destructive fishing practices and changes in water quality). In this particular context, it is crucial to identify and characterize the various factors that promote coral calcification. We thus performed the first investigation of the effect of nickel and urea enrichment on the calcification rates of three coral species. These two factors may indeed interact with calcification through the activity of urease, which catalyzes the hydrolysis of urea to produce inorganic carbon and ammonia that are involved in the calcification process. Experiments were performed with the asymbiotic coral Dendrophyllia arbuscula and, to further assess if urea and/or nickel has an indirect link with calcification through photosynthesis, results were compared with those obtained with two symbiotic corals, Acropora muricata and Pocillopora damicornis, for which we also measured photosynthetic rates. Ambient and enriched nickel (0.12 and 3.50 µg L-1) combined with ambient and enriched urea concentrations (0.26 and 5.52 µmol L-1) were tested during 4 weeks in aquaria. We demonstrate in the study that a nickel enrichment alone or combined with a urea enrichment strongly stimulated urea uptake rates of the three tested species. In addition, this enhancement of urea uptake and hydrolysis significantly increased the long-term calcification rates (i.e. growth) of the three coral species investigated, inducing a 1.49-fold to 1.64-fold increase, respectively for D. arbuscula and P. damicornis. Since calcification was greatly enhanced by nickel in the asymbiotic coral species - i.e. in absence of photosynthesis - we concluded that the effect of increased urease activity on calcification was mainly direct. According to our results, it can be assumed that corals in some fringing reefs, benefiting from seawater enriched in nickel may have advantages and might be able to use urea more effectively as a carbon and nitrogen source. It can also be suggested that urea, for which hotspots are regularly measured in reef waters may alleviate the negative consequences of thermal stress on corals.

The effects of Hurricane Sandy on trauma center admissions.

BACKGROUND: Hurricane Sandy was a particularly unusual storm with regard to both size and location of landfall. The storm landed in New Jersey, which is unusual for a tropical storm of such scale, and created hazardous conditions which caused injury to residents during the storm and in the months following. This study aims to describe differences in trauma center admissions and patterns of injury during this time period when compared to a period with no such storm. METHODS: Data were collected for this study from patients who were admitted to the trauma center at Morristown Medical Center during Hurricane Sandy or the ensuing cleanup efforts (patients admitted between 29 October 2012 and 27 December 2012) as well as a control group consisting of all patients admitted to the trauma center between 29 October 2013 and 27 December 2013. Patient information was collected to compare the admissions of the trauma center during the period of the storm and cleanup to the control period. RESULTS: A total of 419 cases were identified in the storm and cleanup period. 427 were identified for the control. Striking injuries were more common in the storm and cleanup group by 266.7% (p = 0.0107); cuts were more common by 650.8% (p = 0.0044). Medical records indicate that many of these injuries were caused by Hurricane Sandy. Self-inflicted injuries were more common by 301.3% (p = 0.0294). There were no significant differences in the total number of patients, mortality, or injury severity score between the two cohorts. CONCLUSION: The data we have collected show that the conditions caused by Hurricane Sandy and the following cleanup had a significant effect on injury patterns, with more patients having been injured by being struck by falling or thrown objects, cut while using tools, or causing self-inflicted injuries. These changes, particularly during the cleanup period, are indicative of environmental changes following the storm which increase these risks of injury.

Effects of alpha adrenergic blockade and tissue catecholamine depletion on pulmonary vascular response to hypoxia.

The highly reactive pulmonary vascular bed of the neonatal calf was utilized to determine whether the hypoxic pulmonary pressor response is modified by alpha-adrenergic blockade with phenoxybenzamine (Group A) or by tissue catecholamine depletion with reserpine (Group B). In addition, in Group A, the effects of hypoxia on the pulmonary circulation were compared and contrasted with those of l-norepinephrine (alpha-receptor stimulator) and isoproterenol (beta-receptor stimulator). In Group A, changes in pulmonary vascular resistance were calculated from measurements of appropriate pressures and of pulmonary blood flow (electromagnetic flowmeter). The increase in pulmonary vascular resistance produced by hypoxia was not diminished by alpha-adrenergic blockade. However, blockade abolished the pulmonary vasoconstrictor effect of norepinephrine. During hypoxic pulmonary vasoconstriction, the administration of either norepinephrine or isoproterenol lowered the pulmonary vascular resistance both before and after alpha-blockade. While this may be a true vasodepressor effect of these drugs it may also reflect passive changes in the pulmonary vessels secondary to an increased pulmonary blood flow.THE PULMONARY VASCULAR RESPONSE TO HYPOXIA IN THE RESERPINIZED CALVES (GROUP B) WAS TESTED UNDER THREE CIRCUMSTANCES: (1) in the awake animal, (2) in the anesthetized animal prepared in the same way as those in Group A, and (3) during constant flow perfusion of the left lower lobe pulmonary artery. From these studies it was concluded that tissue catecholamine depletion did not diminish the pulmonary vascular response to hypoxia.Thus, neither alpha-adrenergic blockade nor tissue catecholamine depletion prevents the hypoxic pulmonary pressor response. Furthermore, alpha-blockade prevents the pulmonary vasoconstrictor response to norepinephrine but not to hypoxia. Therefore it is concluded that hypoxic pulmonary vasoconstriction is not mediated through adrenergic receptor stimulation or release of endogenous catecholamines.

The red cell mass--arterial oxygen relationship in normal man. Application to patients with chronic obstructive airway disease.

The normal relationship between red cell mass measured, with (51)chromium-labeled red cells, and arterial oxygen saturation (Sa(O2)) over the range from 97.3 to 83.4% was examined by studying 73 normal men residing at sea level and altitudes of 1600 and 3100 m. A simple, linear relationship between Sa(O2) and red cell mass was found over the entire range (r = - 0.7524, P < 0.001). In contrast, a correlation between red cell mass and arterial O(2) tension was found only over the lower half of the range of O(2) tensions where Sa(O2) was also decreased (r = - 0.7731, P < 0.005). This suggested that O(2) saturation rather than tension is the more important determinant of the erythropoietic response to chronic hypoxia. If this response is regulated by tissue O(2) tension, then it will be influenced by O(2) transport, which, in turn, is a function of blood flow and arterial O(2) content, and hence Sa(O2). In nine patients with chronic obstructive airway disease the relationship between red cell mass and Sa(O2) was also determined and was found to be steeper than in the normal subjects (P < 0.05).

Acquired attenuation of chemoreceptor function in chronically hypoxic man at high altitude.

To determine whether chronic exposure to hypoxia during adulthood produces alterations in the control of ventilation, measurements of the resting ventilatory response to hypoxia and hypercapnia, as well as ventilatory response to hypoxia during exercise, were carried out in a group of 10 long-term (3-39 yr) non-native residents of Leadville, Colo. (elevation 3100 m). A group of 8 subjects native to Leadville was also studied and 10 low altitude subjects of Denver, Colo. (elevation 1600 m) served as controls. Hypoxic ventilatory drive was measured as the shape parameter A of isocapnic VE-PA(o2) curves. In the non-native high altitude resident this parameter averaged 43% of the value for low altitude controls (P<0.05) denoting a diminished ventilatory response to hypoxia. The degree of attenuation was related to the length of time spent at high altitude. In the high altitude natives the parameter A averaged 9.6% of control (P<0.01). Similarly hypercapnic ventilatory drive as measured by the slope of the isoxic VE-PA(co2) lines was reduced in the non-native residents to 65% of control (P<0.05) and in the natives averaged 54% of control (P<0.01). In contrast with these findings at rest induction of hypoxia during exercise produced an increase in ventilation comparable to that in the controls in both groups of highlanders. Hence chronic exposure to hypoxia during adulthood in man results in marked attenuation of the ventilatory response to hypoxia at rest and this is a function of the length of exposure to hypoxia. This attenuation of the ventilatory response to hypoxia was associated with a decrease in hypercapnic ventilatory drive. The fact that hypoxic ventilatory drive was almost completely absent while hypercapnic drive was only partially reduced parallels closely the more important role of the peripheral chemoreceptors in mediating ventilatory responses to hypoxia than to hypercapnia. This suggests that the alterations in ventilatory control at altitude are due to failure of peripheral chemoreceptor function.

Hypoxic ventilatory drive in normal man.

A technique is described which permits the inscription of the ventilatory response to isocapnic hypoxia in man as a continuous curve relating alveolar oxygen tension and minute ventilation. The adjustment of ventilation to changes in alveolar oxygen tension is complete in 18-23 sec and this is sufficiently rapid to justify the use of a non-steady-state method. Changes in alveolar carbon dioxide tension are prevented by addition of carbon dioxide to the inspired gas. The resulting [unk]V(E)-P(Ao2) curves are hyperbolic such that falling P(Ao2) produces only slight rises in [unk]V(E) until a critical P(Ao2) range of 50-60 mm Hg is reached. With further fall in P(Ao2), [unk]V(E) increases steeply and the slope of the curve approaches infinity at a tension of 30-40 mm Hg. For purposes of quantitation these curves are approximated by a simple hyperbolic function, the parameters of which are evaluated by a least squares fit of the data. The parameter A denotes curve shape such that the higher the value of A. the greater the increase in ventilation for a given decrease in P(Ao2) and hence the greater the hypoxic drive. Curves are highly reproducible for each subject and curves from different subjects are similar. In 10 normal subjects at resting P(ACo2), A = 180.2 +/-14.5 (SEM). When P(ACo2) is adjusted to levels 5 mm Hg above and below control in six subjects A = 453.4 +/-103 and 30.2 +/-6.8 respectively. These latter values differed significantly from control (P < 0.05). These changes in curve shape provide a clear graphic description of interaction between hypercapnic and hypoxic ventilatory stimuli. At normal P(ACo2) the [unk]V(E)-P(Ao2) curve has an inflection zone located over the same P(o2) range as the inflection in the oxygen-hemoglobin dissociation curve. This indicated that ventilation might be a linear function of arterial oxygen saturation or content. Studies in four subjects have demonstrated that ventilation is indeed related to arterial oxygen content in a linear fashion. These data suggest, but do not prove, that oxygen tension in chemoreceptor tissue as in part determined by circulatory oxygen delivery may be an important factor in controlling the ventilatory response to hypoxia.

Familial prevalence among first-degree relatives of celiac disease in North India.

BACKGROUND AND OBJECTIVES: Prevalence of celiac disease is increased in first-degree relatives with reported prevalence rates in the west between 2.8 and 10%. Paucity of similar data from Asia and the Indian subcontinent prompted us to determine the familial prevalence of celiac disease in first-degree relatives of patients diagnosed with this disorder in Northern India. METHODS: One hundred sixty-nine first-degree relatives (66 parents, 71 siblings and 32 children) of 53 probands were screened by using anti tissue transglutaminase antibodies. Duodenal biopsy was performed in all seropositive relatives and graded as per Marsh classification. Patients with both positive serology and biopsy suggestive of celiac disease were classified as typical celiac disease whereas those with only positive serology were classified as potential celiacs. RESULTS: The prevalence of celiac disease among first-degree relatives was 8.2% (14/169). The prevalence of celiac disease among siblings (15.6%) was much higher as compared to that in parents (3.5%) and offspring (3%). More than one family member was affected in 23% (12/53) of families. Of 14 new cases detected by targeted screening, 11 (78%) were overtly symptomatic with either chronic diarrhoea (8) or easy fatiguability (3). Growth retardation was seen in all six newly diagnosed children, three of whom (22%) were otherwise asymptomatic. Eight members detected to be seropositive had minimal changes on duodenal biopsy (Marsh I and II) suggesting that they have potential celiac disease. CONCLUSION: Familial prevalence of celiac disease in North India is similar to the data from the West. However unlike the situation in the West, the overwhelming majority of first-degree relatives in India are overtly symptomatic with majority having chronic diarrhoea. Since gluten restriction is a highly effective treatment modality, early detection of these patients would result in significant improvement in quality of life as manifested by cessation of diarrhoea and improvement in growth and lab parameters. Our data strongly supports the targeted screening of all first-degree relatives of celiac disease patients in north India.

A comparative study on characterization of textile wastewaters (untreated and treated) toxicity by chemical and biological tests.

Toxicity of textile wastewaters (untreated and treated) and their ingredient chemicals was quantified in terms of their chemical characteristics, fish (Gambusia affinis) mortality and end point growth responses of duckweed (Lemna aequinoctialis) in short-term bioassays. Other parameters of fish bioassay were erythrocyte morphology and its counts. Despite of a definite correlation between data of biological tests (LC/EC(50) values) with that of chemical tests, biological tests were found to be relatively more sensitive to both wastewaters and ingredient chemicals. Amongst all the examined parameters of test organisms, fish RBCs (morphology and counts) sensitivity to pollutants in the wastewaters was usually maximum and therefore, their study should be included in the routine fish bioassay. Other advantage of biological test such as on Lemna is even detection of eutrophic potential of wastewaters, as noted at their higher dilutions. The ingredient chemicals (major) contributing maximum toxicity to textile dye wastewater were, acids (HCl and H(2)SO(4)), alkali (Na(2)O SiO(2)), salt (NaNO(2)) and heavy metal (Cu), whereas dyes (4) were relatively less toxic.

Role of anti cyclic citrullinated peptide antibodies in erosive disease in patients with rheumatoid arthritis.

BACKGROUND & OBJECTIVES: Antibodies to cyclic citrullinated peptide (CCP) are a recently described marker in rheumatoid arthritis (RA), which are said to connote aggressive disease. No data on these antibodies are available from India. We undertook this study to evaluate the role of second generation anti CCP antibodies (anti CCP-2) in predicting erosive disease in Indian patients with rheumatoid arthritis and to define their role in seronegative RA. METHODS: A total of 211 patients with established RA were evaluated in this cross-sectional study for radiographic erosions. A high percentage of seronegative RA patients (40%) were included to assess the role of anti CCP-2 antibodies in this subgroup. Radiographic damage was quantified using modified Sharp score. Apart from anti CCP-2 antibodies, other factors evaluated for their ability to predict erosions included rheumatoid factor (RF) positivity, disease duration, and disease modifying anti rheumatic drugs (DMARD) naïve period. RESULTS: Anti CCP-2 antibodies were seen in 80 per cent patients with RA. Predictors of erosive disease included anti CCP-2 antibody positivity and DMARD naïve period. Patients positive for both RF and anti CCP-2 antibodies had a higher prevalence of erosions as compared to patients positive for only one antibody or negative for both. In seronegative RA (RF absent), anti CCP-2 antibodies were seen in over 50 per cent patients and were associated with a higher incidence of erosive disease. INTERPRETATION & CONCLUSION: Our finding showed that anti CCP-2 antibodies were present in 80 per cent patients with established RA. These have an independent role in predicting erosive disease, especially in the seronegative subgroup.

Collapsing glomerulopathy associated with hepatitis B infection: A case report.

Collapsing glomerulopathy has been classified as a variant of focal segmental glomerulosclerosis. It is associated with infections, inflammations, and certain medications. While its association with human immunodeficiency virus has been well established its occurrence with hepatitis B has not been reported. We present here a case of collapsing glomerulopathy in a child with hepatitis B infection.

The coronary stress of skiing at high altitude.

Skiing, which may involve strenuous exercise in the cold at high altitude, could place considerable stress on the coronary circulation. To explore this possibility, we obtained by telemetry electrocardiograms on 149 men during recreational skiing at altitudes above 3100 m (10 150 ft). Tachycardia was impressive; heart rate exceeded 80% of predicted maximum in two thirds of the subjects. Five men developed abnormal ST-segment depression during or immediately after exercise. All five were older than 40 years, so in this age group the incidence of ST abnormalities was 5.6%. This is not greater than the incidence among asymptomatic men during submaximal exercise at low altitude. The high level of physical fitness of men who ski may have offset the added stress of cold and hypoxia. Hence, for physically fit older men, mountain skiing does not appear to pose a greater coronary stress than does comparable exercise at low altitude among men of only average physical fitness without known heart disease.

Cedecea lapagei in a patient with malignancy: Report of a rare case.

Cedecea lapagei is a member of the family Enterobacteriaceae and is an uncommon pathogen. There are very few reports of isolation of this organism from biological samples; mostly it is found to be a pathogen in elderly or otherwise medically compromised. We present a rare case of a patient with underlying malignancy of buccal mucosa, who developed an oral ulcer superinfected with C. lapagei. According to the available literature, this is the first case of C. lapagei from India detected in a cancer patient.

Rhabdomyosarcoma infiltrating bone marrow.

We present a case of 26-year-old male, previously diagnosed as rhabdomyosarcoma (RMS) of perineal region. The peripheral smear showed a leukoerythroblastic picture with an occasional atypical cell. The bone marrow aspirate and biopsy showed monotonous sheets of malignant cells. On immunohistochemistry the tumor cells were strongly positive for desmin and negative for CD34 and CD117. This case illustrates the morphology and IHC findings in a case of RMS. Immunostains like CD34 and CD117 should be included to rule out a possibility of acute leukemia.

Pharmacokinetics of the nitric oxide synthase inhibitor L-NG-methylarginine hydrochloride in patients with septic shock. Glaxo Wellcome International Septic Shock Study Group.

OBJECTIVES: To characterize the pharmacokinetics of L-NG-methylarginine in patients with septic shock. METHODS: This was an international, uncontrolled, open-label study of L-NG-methylarginine (546C88) therapy given to 32 patients with septic shock. It was conducted in hospital-based intensive care units that admit general surgical and medical patients. Patient cohorts received an infusion of L-NG-methylarginine at fixed dose rates of 1, 2.5, 5, 10, and 20 mg/kg/h for up to 8 hours. The 5 dosing regimens were administered sequentially to separate groups of patients. RESULTS: Of the 32 patients studied, 23 received complete 8-hour infusions. In the other 9 patients, the infusion was terminated prematurely within the first 1/2 to 4 hours. Median clearance of L-NG-methylarginine averaged 485 mL/h/kg for the 1 and 2.5 mg/kg/h dosing cohorts combined but decreased to 283, 181, and 98 mL/h/kg for the 5, 10, and 20 mg/kg/h dosing cohorts, respectively. Median renal clearance was similar at 9 to 26 mL/h for the 1, 2.5, and 5 mg/kg/h dosing cohorts but increased to 156 and 284 mL/h for the 10 and 20 mg/kg/h dosing cohorts, respectively. Median steady-state volume of distribution was similar in all 5 dosing cohorts, averaging 0.66 to 0.82 L/kg. CONCLUSIONS: The 80% decrease in clearance from 485 to 98 mL/h/kg with the increase in dose suggests that a predominant metabolic pathway(s) of L-NG-methylarginine, accounting for at least 80% of clearance, is becoming progressively saturable in association with L-NG-methylarginine infusion rates > or = 5 mg/kg/h. Therefore the use of L-NG-methylarginine infusion rates > or = 5 mg/kg/h are typically expected to result in progressive inhibition of nitric oxide synthase activity. Consequently, patient hemodynamics should be monitored closely to avoid an excessive increase in vasomotor tone, which would be manifest by either an increase in mean arterial pressure or a decrease in cardiac output. The infusion rates of conventional vasopressor(s) (eg, norepinephrine [BAN, noradrenaline]) or L-NG-methylarginine or both may need to be reduced accordingly.

Bronchoconstriction and pulmonary hypertension during abortion induced by 15-methyl-prostaglandin F2alpha.

Patients have experienced severe breathlessness during second trimester abortion initiated by the intramuscular injection of 15-methyl-prostaglandin F2alpha (15-me-PGF2alpha). In four healthy women given 400 mug of 15-me-PGF2alpha to induce abortion, pulmonary function tests showed reductions in arterial oxygen tension, maximum expired air flow and vital capacity. Residual lung volume and the slope of phase III of the closing volume curves increased.