Usage Pattern of Fixed-dose Combinations at ICMR Network of Rational Use of Medicine Centres across India: Recommendations for Policymakers and Prescribers.

AIM: Irrational use of medicines is a global problem. In India, one contributing factor is the availability of a large number of fixed-dose combinations (FDCs). To improve rational use and to strengthen policies, it is important to assess the usage patterns and rationality of FDCs. METHODS: This study was conducted as part of a 1-year prospective cross-sectional analysis of prescriptions in the outpatient clinics of broad specialities from 13 tertiary care hospitals across India. Five most commonly prescribed FDCs in each center were analyzed. In addition, all the prescribed FDCs were classified as per the Kokate Committee classification and it was noted whether any of the FDCs were irrational or banned as per the reference lists released by regulatory authorities. RESULTS: A total of 4,838 prescriptions were analyzed. Of these, 2,093 (43.3%) prescriptions had at least one FDC. These 2,093 prescriptions had 366 different FDCs. Of the 366 FDCs, 241 were rational; 10 were irrational; 14 required further data generation; and the remaining 96 FDCs could not be categorized into any of the above. Vitamins and minerals/supplements, antibacterial for systemic use, and drugs for gastroesophageal reflux disease (GERD) and peptic ulcer were the most used FDCs. CONCLUSION: Based on the finding that some prescriptions contained irrational FDCs, it is recommended that a rigorous, regular, and uniform method of evaluation be implemented to approve/ban FDCs and that prescribers be periodically notified about the status of the bans.

Enhancer-deficient amphotropic murine leukemia virus and recombinants with heterologous transcription elements can be efficiently amplified and detected in Mus dunni fibroblasts.

Amphotropic murine leukemia virus (MLV) replicates in cells from various mammalian species, including humans, and is a potential contaminant in MLV vector preparations for human gene transfer studies. Mus dunni fibroblasts are routinely used for amplification and detection of contaminating virus. We have recently characterized an amphotropic MLV mutant lacking the 75-bp viral enhancer elements and spontaneous MLV-(RCMV) recombinants that have acquired cytomegalovirus (CMV) transcription elements. Both of these viruses replicate in specific human cell types. To test whether the formation of such viruses can be detected and controlled with current routine procedures, we have analyzed the replication of these amphotropic MLV mutants in Mus dunni fibroblasts. We find that M. dunni cells are permissive for enhancer-deficient and CMV promoter-recombinant MLV from several human cell lines. Thus, M. dunni fibroblasts are suitable for the amplification and subsequent detection of enhancer-deficient and enhancer-recombinant MLV in vector preparations.

Experience with small-incision and conventional cholecystectomies in a community hospital

We reviewed the results of 25 small-incision cholecystectomies and 79 conventional cholecystectomies performed at Visayas Community Medical Center from January 1, 2000 to January 31, 2002. There were no differences in the mean age and the male to female ratio in both groups. The mean duration of operation for the small-incision cholecystectomy group was 132.2 minutes while it took 133.4 minutes in the conventional cholecystectomy group. Resumption of regular diet in the small-incision cholecystectomy group was 2.5 days while it took 4 days in the conventional cholecystectomy group. Postoperative hospital stay ranged from 3 to 6 days with a mean of 4 days in the small-incision cholecystectomy group. On the other hand, postoperative hospital stay ranged from 4 to 10 days with a mean of 7.3 days in the conventional cholecystectomy group. Complications seen included postoperative fever, intraoperative bleeding, wound infection and bile leak. Overall, our study confirmed the earlier resumption to regular diet and shorter postoperative stay, thus, faster recovery in the small-incision cholecystectomy group. However, no conclusion can be made because of limitations in the study design and the small sample size. (Author)

Replication of enhancer-deficient amphotropic murine leukemia virus in human cells.

Amphotropic murine leukemia virus (MLV) replicates in cells from various mammalian species, including humans, and is a potential contaminant in MLV vector preparations for human gene transfer studies. The generation of replication-competent virus is considered less likely with vectors that delete the viral transcription elements. This conclusion is based on data obtained in rodents, where MLV replication depends on the expression of viral genes under the control of 75-bp enhancer elements in the long terminal repeat. We demonstrate here that in some human cells replication of amphotropic MLV is possible in the absence of these enhancer elements. Replication of the enhancer-deficient virus MLV-(MOA)Delta E is observed in selected human sarcoma and B lymphoma lines and proceeds at a lower rate than that of the intact virus. No insertion of a foreign promoter or enhancer into the long terminal repeat was detected. Our data suggest the presence of a secondary enhancer element within the MLV provirus that can in selected human cells mediate virus transcription and replication in the absence of the 75-bp U3 enhancers.

Amphotropic murine leukemia virus replication in human mammary epithelial cells and the formation of cytomegalovirus-promoter recombinants.

Amphotropic murine leukemia virus (MLV) can replicate in human cells and is a potential contaminant in vector preparations for human gene transfer studies. We have recently shown that replication of amphotropic MLV in specific human sarcoma and lymphoma lines is possible in the absence of the viral 75-bp transcription enhancer elements. Here, we have tested the replication of an amphotropic MLV, MLV-(MOA), and an enhancer-deficient mutant of this virus in human breast carcinoma-derived cell lines. The proviral expression plasmids use a cytomegalovirus (CMV) promoter for the initial transcription of virus RNA. We found that all cells analyzed are permissive for replication of MLV-(MOA). Enhancer-deficient virus is unable to replicate. However, in two lines the replication defect can be rescued by the spontaneous insertion of a CMV promoter and enhancer into the U3 region. This recombinant virus MLV-(RCMV) replicates with kinetics similar to that of MLV-(MOA) but is restricted to specific cell lines. The potential formation of RCMV recombinants during MLV vector preparation must be considered.

Cleanup procedure for monitoring chlorinated compounds in animal feed and crops.

A powerful cleanup procedure for determination of chlorinated pesticides and polychlorinated biphenyls (PCBs) in difficult agricultural matrixes like feeds or crops was developed to eliminate the interferences in chromatograms obtained by gas chromatography with electron capture detection. The adsorption material used was ENVI-Carb, a graphitized nonporous carbon material. This procedure proved to be more reliable than the established cleanup procedure, which uses gel permeation chromatography and silica gel cartridges. Because ENVI-Carb cleanup delivers clear, colorless eluates with no interferences, chlorinated pesticides and PCBs may be detected at levels as low as 0.0004 mg/kg for monitoring purposes. Accuracy was validated through a series of recovery experiments.

Percutaneously implantable catheter-port system: preliminary technical results.

The function and safety of a percutaneously implantable catheter-port system were studied in 44 patients with different diseases (32 patients with malignant disease, 11 with peripheral arterial disease, and one with recurrent asthmatic attacks). Most patients required repeated local-regional arterial infusion. Infection (two patients) and catheter-related complications (10 patients) were observed during the follow-up period (maximum length of follow-up, 542 days; mean, 177 days). Port migration or leakage did not occur. The data suggest that this new catheter-port system is safe and easy to handle.

Early diagnosis of perinatal cerebral lesions in apparently normal full-term newborns by ultrasound of the brain.

The brains of 1000 consecutive, clinically normal, full-term neonate without signs of perinatal distress were examined by ultrasound 3 days postpartum. We found 35 cases of intracranial haemorrhage (periventricular, choroid plexus and intraventricular); 34 possible sequelae of bleeding (subependymal and choroid plexus pseudocysts; local dilatation of the lateral ventricles) and 21 morphological aberrations. Most of these 90 abnormalities were checked several times. Four children with intracranial haemorrhage developed symptoms (3 hemipareses, 1 infantile spasm) within a year of birth. No child without sonographic abnormalities has so far been recognized as developing a clinical deficit.

[The frequency of the combination of arterial occlusive disease in supraaortic and leg range. An analysis in the patient population of a vascular surgical department (author's transl)]. / Zur Häufigkeit der Kombination von arterieller Verschlusskrankheit im supraaortischen und Becken-Bein-Bereich im Krankengut einer gerfässchirurgischen Abteilung.

Among 337 male patients who were hospitalized because of chronic ischemia of the leg, 103 (=30.6%) were shown to suffer from concomitant occlusive vascular disease of supraaortic branches. This was evaluated by simple examination like auscultation, bilateral blood pressure measurements, and palpation of pulses. In 52% the patients history revealed dizziness, hemiparesis and transient ischemic attacks (TIA). Arteriell hypertension promotes supraaortic vascular diseases as is shown by a relative frequency of 0.52 in contrast to 0.39. Combined occlusions of the iliac and femoropopliteal arteries are accompanied by supraaortic vascular disease in 40%, in femoropopliteal occlusion alone in only 20%. If the basic diagnostic approach is improved by directional ultra-sonic examinations of the carotid arteries, approximately 20% of all patients with advanced vascular disease of the iliac and femoropopliteal arteries have to be operated on for cerebrovascular disease.

[More safety in catheter cerebral angiography (author's transl)]. / Mehr Sicherheit in der zerebralen Katheter-Angiographie

Hazards and difficulties of catheter carotid and vertebral angiography are reported. Our experience is based on 257 persons who had undergone 338 carotid and 33 vertebral arteriographies. In 31 patients, bilateral carotid as well as aortic arch and abdominal aortic, iliac and lower limb arteriography were carried out in one session. Our material consists of consecutive cases. The characteristics of the "sidewinder-technique" are emphasized. Several safety measures considered necessary during the examination are described.

[Results of reconstructive procedures concerning occlusive arterial disease of the full length of the trifurcation of the lower limb (author's transl)]. / Ergebnisse rekonstruktiver Eingriffe bei arterieller Verschlusskrankheit vom langen Trifurkationstyp

42 vascular reconstructive procedures, concerning occlusions in full length of the trifurcation of the lower limb, were carried out in 40 patients. The success-rate was unsatisfactory. It was as low as 55% after 30 days and 25% after 28 months. This is thought to be due to wrong indication and unfavorable operative proceedings. The high hospital letality of 12%, observed in aged persons only, may be reduced by improving post-operative care. It is stressed that any bad result of this kind of vascular surgery is connected with a high vital danger to the patient in question. Avoiding pre- and intraoperative unfavorable factors is rewarded by better early result; thus it is not the method itself but its wrong application which is bad.

[Mammographic observations on the growth of untreated cancer of the breast (author's transl)]. / Mammographische Beobachtungen über den Verlauf des unbehandelten Mammakarzinoms

Report on 21 primary breast cancers in 19 untreated women. The longest follow-up was 1074 days, the shortest 24 days. Doubling time of the tumors was calculated with Collins formula. The necessary assessment of the volume of tumors was calculated with a simple method. Doubling time differs greatly and, in parts, greatly exceeds published data. The radiologic development is surveyed. Collins formula is discussed in its strict interpretation starting from the volume of one tumor cell. Our own results lead to conclusions on the radiologic diagnosis of breast cancer. Usually diagnosis is immediately followed by therapy. Observations on the spontaneous course of, expecially primary, cancer of the breast are therefore scanty. Larger numbers of repeated mammography of the same tumor do not exist. Clinical examinations of growth belong to earlier times, the patients even to past centuries (Bloom 1964). Systematic investigations of this type cannot be defended on ethical grounds. In order to acquire insight into spontaneous growth of this cancer one has to rely on the few cases in whom operation wa5 not done for various reasons Here repeat mammography was possible. Such cases are important in practice since repeat mammography may have to be recommended by the radiologist, our own material will be discussed.

[The cervical collateral network in subclavian steal syndrome and block of the vertebral artery (author's transl)]. / Das zervikale kollaterale Netzwerk bei Subklavian Steal Syndrom und Verschluss der A. vertebralis

A case of rightsided subclavian steal syndrome and block of the right vertebral artery is reported. The importance of the collateral cervical network is emphasized. The diagnostic criteria of a steal phenomenon in the area of the branches of the aorta are discussed.

[Early showing of veins in arteriography of the lower limbs (author's transl)]. / Frühzeitige Venendarstellung bei der Arteriographie der unteren Extremität

Report on incidence, frequency and localization of early venous filling of the leg in 518 aorto-arteriograms. No relationship to arterial block could be found. The data suggest that premature venous filling is a phenomenon influenced by various factors which cannot be connected with any constant entity and has no diagnostic value.

[Chronic traumatic arteriovenous fistulae (author's transl)]. / Chronische traumatische arteriovenöse Fisteln

In two patients with femoral arterio-venous fistulae angiography could show arterial and venous collaterals with differing circulation phases. When angiography shows retrograde flow in the artery distal to the fistula, the volume of arterial collateral circulation is unrelated to the peripheral blood-supply. Venous collateral circulation has to be included in the fistular circulation. Angiography permits distinguishing a venous by-pass circulation for the return of blood from the periphery. In one patient a large aneurysm of the iliac vein was found. Special features of angiography, particularly after surgical closure of the fistula, are mentioned.

[Experience with the Contrac III syringe in carotid angiography (author's transl)]. / Erfahrungen mit der Contrac-III-Spritze bei der Karotisangiographie

Report on a comparison between the use of the Contrac III syringe and manual injection for carotid angiography. 100 cases of injector angiograms were compared with 100 unselected manual arteriograms. The injector angiograms needed less contrast fluid and were distinctly better than the manual angiograms. Evaluation was based on the frequency of visualization of the posterior cerebral artery, the anterior cerebral arteries on either side and the filling of lenticulostriary vessels. Using the injector raises the percentage of bilateral filling of the anterior cerebral artery; the posterior cerebral artery, too, is rendered visible much more often. The quality of filling of the basal arteries depends largely on the speed of the injection. According to our present experience complications with the injector are no more frequent than with manual injection. Injection with the Contrac III syringe is, therefore, a definite advance, since it permits producing angiograms of very good, even, reproducible quality.