CLINICO-EPIDEMIOLOGICAL ALGORITHM FOR PREDICTING SYSTEMIC ARTERIAL HYPERTENSION AT HIGH ALTITUDE THROUGH MATHEMATICAL MODELLING

A population based hybrid design combining element of cohort and cross-sectional approach was used to develop a simple clinical algorithm to predict individual probability of developing hypertension (systolic BP > 140 mm Hg and/or diastolic BP > 90 mmHg). 3615 soldiers initially normotensive at the time of induction into high altitude, were studied by systematic random sampling. Multiple logistic regression analysis showed a high significant association between hypertension and age, body mass index (BMI), tobacco smoking and alcohol consumption. Using the constant/coefficient values obtained from the logistic model and the receiver operating characteristics (ROC) curve analysis, the following predictive rule was developed – To the age in years, add (BMIx 3.86); also add 5.53 if he is a smoker; and add 19.81 if he consumes alcohol. If the total exceeds 142, the individual is at high risk of developing hypertension. This algorithm carries a sensitivity of 68.2% and specificity of 78.5%.KEY WORDS: Hypertension, High altitude     

Misoprostol as aid in First Trimester MTP

Background

Medical Termination of Pregnancy (MTP) is a commonly performed during the first trimester. Dilatation and Evacuation (D & E) mandates rapid dilatation of cervix with metal dilators, which requires anaesthesia and may be associated with trauma to the uterus, cervix and later cervical incompetence. The problem of rapid cervical dilatation is obviated with intravaginal misoprostol.

Methods

Intravaginal misoprostol tablet 200 microgram was inserted, a night prior to MTP to ripen the cervix. Cervix was dilated with metal dilators only in cases where cervix did not loosen up sufficiently. Products of conception were removed by suction.

Results

Out of 108 cases cervical dilatation was not required in 96 cases (88.9%).

Conclusion

Intravaginal misoprostol 200 microgram proved effective as a priming agent prior to MTP in the first trimester.Key Words: Misoprostol, MTP     

Progesterone receptors A and B differentially modulate corticotropin-releasing hormone gene expression through a cAMP regulatory element

Corticotrophin-releasing hormone (CRH) plays a major role in mechanisms controlling human pregnancy and parturition. Gene regulation by progesterone may be a key point in the control of placental CRH production. Studies in primary placental ceils show that antagonism of progesterone activity or production by RU486 or trilostane leads to an increase in CRH promoter activity. This effect can be reversed by the addition of progesterone. Overexpression of progesterone receptor A (PRA) or glucocorticoid receptor resulted in a decrease in CRH promoter activity following progesterone treatment, whereas an increase in promoter activity was observed with overexpressed PR-B.     

Estrogen receptor-mediated down-regulation of corticotropin-releasing hormone gene expression is dependent on a cyclic adenosine 3＇ ,5＇-monophosphate regulatory element in human placental syncytiotrophoblast cells

Placental CRH plays a major role in the mechanisms controlling human pregnancy and parturition. Understanding how placental CRH production is regulated is therefore of importance. Previously we have shown that placental expression of CRH peptide and mRNA are inhibited by estrogens, in contrast to the stimulatory effects of estrogen on hypothalamic CRH production. Our current study found that in placental cells cotransfected with a CRH promoter construct and an estrogen receptor-alpha expression vector results in a differential regulation whereby 17beta estradiol (E2) decreased and the putative pure estrogen antagonist, ICI 182780,     

Sustained activation of p38 mitogen-activated protein kinase contributes to the vascular response to injury

The vascular response to mechanical injury involves inflammatory and fibroproliferative processes that result in the formation of neointima and vascular remodeling. The complex cellular interactions initiated by vascular injury are coordinated and modulated by the elaboration of cytokines and growth factors. The production and transduction of many of these mediators require phosphorylation of p38 mitogen-activated protein kinase (MAPK). In the present investigation, we examined the pattern and localization of p38 MAPK activation following balloon vascular injury. The effects of long-term and selective inhibition of p38 MAPK with SB 239063 (trans-1-(4-hydroxycyclohexyl)-4-(4-fluorophenyl)-5-[2-methoxy)pyrimidin-4-yl]imidazole) were also investigated in a model of vascular injury. Western blotting and immunohistochemical staining demonstrated that phospho-p38 MAPK was increased following balloon injury of the rabbit iliofemoral artery. The p38 MAPK activation was noted as early as 15 min after balloon injury and remained elevated for at least 28 days. Phospho-p38 MAPK immunoreactivity (IR) was localized primarily in regions of dedifferentiated, smooth muscle alpha-actin-positive cells in all lamina of the vessel wall. Phospho-p38 MAPK IR was not correlated with the localization of macrophage or proliferating cells (proliferating cell nuclear antigen; PCNA +). Long-term treatment (4 weeks) with SB 239063 (50 mg/kg/day, p.o.) reduced the vascular response to injury in the hypercholesterolemic rabbit. SB 239063 had no effect on platelet-derived growth factor (PDGF)-stimulated migration or proliferation of rabbit vascular smooth muscle cells (VSMCs) in culture. However, SB 239063 produced a concentration-dependent inhibition of transforming growth factor (TGF)-beta-stimulated fibronectin production in VSMCs. In conclusion, sustained activation of p38 MAPK plays an important role in the vascular response to injury and inhibition of p38 MAPK may represent a novel therapeutic approach to limit this response.     

Growth hormone therapy for protein catabolism

GH and IGF-I have shown remarkable consistency of effect in a wide range of catabolic conditions. Doses of around 10 IU/m2/day of GH and 80 micrograms/kg/day of IGF-I over short periods of time can improve net protein synthesis and preserve lean body mass. Most studies have reported metabolic endpoints, but favorable clinical effects have included decreased hospital stay and mortality in burns, improved respiratory muscle function in COAD, preserved grip strength post- operatively, and improvements in cardiac and bowel failure. Adverse effects of GH treatment are uncommon and usually related to glycaemic control. GH and IGF-I have differential effects on insulin concentrations--increasing or decreasing concentrations, respectively. The hypoglycaemic effects of IGF-I are dependent on route of administration and are avoided by subcutaneous delivery. Occasional patients have needed to discontinue GH treatment due to hyperglycaemia, although the anabolic action of GH may be partially mediated by increased insulin levels. The co-administration of GH and IGF-I has theoretical advantages by both increasing IGF binding-protein concentrations and balancing glycaemic control. An initial study with combination therapy in calorically-restricted volunteers has shown anabolic effects greater than with either agent alone. This approach requires further study in catabolic patients. There is a need for large, well-designed trials with clinical rather than purely metabolic end-points, and some of these are already underway. Should these studies confirm the early findings, financial considerations will become paramount, although it remains possible that treatment may be self-financing if lengths of hospital admissions are shortened.      

EFFICACY OF TWICE-DAILY AMOXYCILLIN/CLAVULANATE (‘AUGMENTIN-DUO’ 400/57) IN MILD TO MODERATE LOWER RESPIRATORY TRACT INFECTION IN CHILDREN

SUMMARY A new amoxycillin/clavulanate regimen (‘Augmentin-Duo’ 400/57), to be given orally in two divided doses, has been proposed to overcome the inconvenience of tid dosing. This observer-blind, multicentre study randomised children aged two to 12 years with lower respiratory tract infection to seven days' treatment with either amoxycillin/clavulanate bid at a dose of 25/3.6mg/kg/day (221 patients) or the currently prescribed amoxycillin/clavulanate regimen of 20/5mg/kg/day tid (216 patients). Clinical success (cure) rates at follow up were 81.0% for the bid group and 77.8% for the tid group [difference 3.2%; 95% CI (-4.36, 10.80)], indicating that the regimens were of equivalent efficacy. Both regimens were well tolerated, and there was no statistically significant difference in the incidence of adverse experiences between the two groups. Compliance with study medication was high and similar for both groups (80% compliance: bid 90.0%; tid 87.0%).     

OFLOXACIN VERSUS TRIMETHOPRIM AND CO-TRIMOXAZOLE IN THE TREATMENT OF UNCOMPLICATED URINARY TRACT INFECTION IN GENERAL PRACTICE

A large-scale, randomised, multicentre single-blind clinical trial was conducted to assess the comparative efficacy and tolerance of ofloxacin, trimethoprim and co-trimoxazole in the treatment of uncomplicated urinary tract infection in general practice. A total of 1,069 patients from 76 centres across the UK were enrolled in the study, and randomised to one of the following treatment groups: ofloxacin (200 mg od), trimethoprim (200 mg bd) or co-trimoxazole (trimethoprim 160 mg and sulphamethoxazole 800 mg bd). Each patient received five days of medication. Clinically, ofloxacin was as effective as trimethoprim and co-trimoxazole. However, the bacteriological cure rate was significantly better for ofloxacin, with eradication of the initial causative pathogen by the end of treatment in 92% of patients in the ofloxacin group, compared with 81% for trimethoprim and co-trimoxazole (P = 0.0002). There was also a lower relapse rate for ofloxacin. Ofloxacin was well tolerated: adverse events were reported by 67 (12.4%) patients in the ofloxacin group, compared with 48 (18.7%) patients in the co-trimoxazole group and 37 (13.6%) patients in the trimethoprim group. Ofloxacin can therefore be considered a suitable alternative for the treatment of uncomplicated urinary tract infection.     

Cytogenetic studies in patients with secondary leukemia/dysmyelopoietic syndrome after different treatment modalities

Cytogenetic studies of 68 patients who developed secondary leukemia (SL)/dysmyelopoietic syndrome (DMS) after extensive chemotherapy and/or radiation therapy as well as patients who developed SL/DMS without such treatment showed that those patients who received radiation alone or with chemotherapy had more extensive numerical and structural abnormalities than those who received only chemotherapy. In terms of the specific chromosomal abnormalities, there are no differences between the various treatment groups. Hypodiploidy is the most common form of aneuploidy in these patients, with the most common numerical abnormality being the loss of chromosome 7. The most common structural abnormalities involved chromosomes 3 and 5. When compared with patients with de novo leukemia and DMS, the chromosomal abnormalities in these patients are more complex and extensive. Serial studies revealed that cytogenetic abnormalities do not precede the development of hematologic changes by significant time periods.