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Oxygen dynamics in crude oil contaminated salt marshes: I. Aerobic respiration model.

A simple model was developed to predict oxygen demand exerted by aerobic biodegradation of spilled crude oil and fertilizer added to stimulate biodegradation in salt marsh sediment. The role of aerobic respiration (AR) was determined using first-order G kinetics. The G kinetic rate constants were calculated from laboratory data sets through linear regression. The effect of oil and fertilizer on AR was quantified by comparing three treatments: (i) control (no oil and fertilizer amended), (ii) fertilized, and (iii) oiled and fertilized sediments. The effects of dissolved oxygen concentration in the overlying water and surface mass transfer coefficient were investigated. Aerobic respiration was strongly dependent on the overlying dissolved oxygen concentration when crude oil and fertilizer were added. Oiled/fertilized cores did not show higher SOD and AR than control cores when overlying DO concentration dropped below 5 mg l(-1). Results indicate that higher aerobic respiration in oiled/fertilized is exerted by aerobic biodegradation of crude oil and that major biodegradation of crude oil occurs only when DO level is high (> 5 mg l(-1)).

Accidents↗

Sexual behaviour in travellers abroad attending an inner-city genitourinary medicine clinic.

OBJECTIVE: To investigate frequency of sexual encounters with new partners abroad in patients attending a genitourinary clinic (GUM). METHODS: In a case series 464 attenders at a genitourinary medicine clinic completed an anonymous self-administered questionnaire, if they had been abroad recently, enquiring about sexual behaviour abroad. RESULTS: 28.4% of subjects admitted to sex with a new partner abroad with only 41.7 per cent consistently using condoms. There were no significant differences in condom use for gender, ethnicity or type of visit and relationship. Twenty-nine per cent of those admitting to sex abroad had more than one partner. The risk of multiple partners was not associated with gender, ethnicity, type of visit (holiday or business) or type of relationship (heterosexual or homosexual). The first partner abroad for 63% of men and 62.5% of women was of a nationality other than that of United Kingdom residents. Non-Caucasians and homosexuals were significantly more likely to have first partners abroad from outside the UK than Caucasians and heterosexuals respectively. CONCLUSION: The occurrence of casual sex abroad in GUM attenders suggests that further research is needed to establish targetable risk factors for this type of behaviour amendable to change through health promotion.

Adolescent↗

[Authorization, institutional services, hospital-based practices and cooperation in the hospital--from the point of view of the hospital owners].

Structural changes in the financing of hospital-based health care in Germany make a revision of the currently existing strict separation between ambulatory and stationary patient care inevitable. The present monopolist situation of office-based physicians (organised in private practices without any legal or financial relation to a hospital) will be amended by the participation of hospitals and hospital-employed doctors in ambulatory services of a different kind. These may include the institutional authorization of hospitals to participate in ambulatory services, especially in the case of emergencies and first aid, and co-operations between doctors in private practices and hospitals. Such co-operations are now legally enabled to provide "integrated services", but still lacking acceptance by the parties involved in the health care services. Ambulatory medical care is an already huge and now rapidly growing market, whereas the classical hospital services represent a declining product. Therefore hospitals will have to act accordingly or they will even forfeit the opportunity to use the ambulatory care sector to improve the intensity of utilisation of their hospital beds. In addition, hospitals will have to accept that office-based doctors are their customers and have to be treated as such. The establishment of regional networks may be a solution to this problem. Integrated services can only be established if new ways of co-operation and knowledge transfer are introduced into this area step by step. The present article provides practical examples of co-operation models.

Germany↗

Effect of chemical and microbial amendments on ammonia volatilization from composting poultry litter.

Research has shown that aluminum sulfate (alum) and phosphoric acid greatly reduce ammonia (NH3) volatilization from poultry litter; however, no studies have yet reported the effects of these amendments on field-scale composting of poultry litter. The objectives of this study were to (i) evaluate NH3 volatilization from composting litter by measuring both NH3 volatilization and changes in total nitrogen (N) in the litter and (ii) evaluate potential methods of reducing NH3 losses from composting poultry litter. Poultry litter was composted for 68 d the first year and 92 d the second year. Eleven treatments were screened in Year 1, which included an unamended control, a microbial mixture, a microbial mixture with 5% alum incorporated into the litter, 5 and 10% alum rates either surface-applied or incorporated, and 1 and 2% phosphoric acid rates either surface-applied or incorporated. Treatments in Year 2 included an unamended control, a microbial mixture, alum (7% by fresh wt.), and phosphoric acid (1.5% by fresh wt.). Alum and phosphoric acid reduced NH3 volatilization from composting poultry litter by as much as 76 and 54%, respectively. The highest NH3 emission rates were from microbial treatments each year. Compost treated with chemical amendments retained more initial N than all other treatments. Due to the cost and N loss associated with composting poultry litter, composting is not economical from an agronomic perspective compared with the use of fresh poultry litter.

Air Pollutants↗

Ragsdale v. Turnock, 10 March 1988, as amended on 13 April 1988.

The plaintiffs, physicians and women seeking abortions, challenged licensing regulations imposed by the state of Illinois on abortion clinics. The Court found the following requirements to place unconstitutional burdens on a woman's right to obtain an abortion: 1) that separate licenses be obtained for facilities devoted primarily to performing first trimester abortions; 2) that a physician who was to perform an abortion also perform a pregnancy test, even if such a test had already been performed by another physician; 3) that persons undergoing abortions be given counseling which includes a discussion of alternatives, a description of procedures, and an explanation of risks and possible complications; 4) that physicians providing preabortion counseling not be involved financially in the woman's decision; 5) that facilities performing abortions comply with the physical plant and staffing provisions of the Illinois Ambulatory Surgery Treatment Center Act; and 6) "certificate of need" proceeding requirements of the Health Facilities Planning Act. In 1988, other US Courts reached the following decisions with respect to the licensing of abortion clinics: 1) a building inspector had violated the right of privacy of women to obtain abortions by classing an outpatient abortion clinic as a hospital, thereby forcing it to obtain a special-use permit to operate in the zone where it was to be sited (P.L.S. Partners, Women's Medical Center of Rhode Island, Inc. vs. City of Cranston, US District Court, D. Rhode Island, 28 June 1988 [696 F.Supp. 788]) and 2) a physician who is prevented from operating an abortion clinic by unconstitutional zoning ordinances can bring a personal civil rights action under federal law for monetary damages, and those who enacted the ordinances are not absolutely immune from liability if the purpose of the ordinances was to single out an individual and treat that individual differently from others (Haskell vs. Washington Township, United States Court of Appeals, Sixth Circuit, 20 December 1988 [864 F.2d 1266]).

Abortion, Induced↗

Introduction to the Food and Drug Administration (FDA) regulatory process.

FDA oversight of medical devices, including in vitro diagnostic devices (IVDs or laboratory tests), in the United States was a direct result of the passage of the Medical Device Amendments of 1976. This law introduced a series of general controls for medical devices including registration and listing, requirements for production using good manufacturing practices, and requirements for post-market reporting of device failures. This produced for the first time a menu of laboratory tests on the market, a system to ensure these were produced consistently over time, and a mechanism for FDA to identify problems with device use and to work with companies to ensure corrective action. This law also introduced the requirement for premarket review of new versions of old devices and of fundamentally new medical devices.

Animals↗

New federal policy for children with special health care needs: implications for pediatricians.

Title V of the Social Security Act of 1935 established the nation's first categorical health care program for children: the Crippled Children's Service. In 1985, federal legislation changed the name of the Crippled Children's Service to the Program for Children With Special Health Care Needs. Four years later, new amendments to Title V dramatically altered the Program's mission. States are now required to spend 30% of the funds from the Maternal and Child Health Services block grant on children with special health care needs and to take specific steps toward improving the service system for these children and their families. The new mandate is the only current foundation of a national health policy for children with special health care needs. The 1989 law substantially broadens the mission of the state programs and explicitly recognizes that all children with a special health care need should have access to an appropriate, community-based system of care monitored by state Children with Special Health Care Needs agencies. In addition, states are now required to conduct needs assessments pertaining to these children, to foster local systems of care, and to ensure a high quality of community-based services. Understanding the implications of the new amendments is essential because pediatricians and other child health care professionals have key roles to play in implementing these new policies.

Child↗

City of Revere v. Massachusetts General Hospital: government responsibility for an arrestee's medical care.

City of Revere v. Massachusetts General Hospital presented the United States Supreme Court with its first opportunity to consider whether a state or municipality has a constitutional duty to pay for medical treatment received by an individual in police custody. The Supreme Judicial Court of Massachusetts had held that the city had an eighth amendment duty to pay for an arrestee's treatment. The U.S. Supreme Court reversed, observing that eighth amendment rights and duties are not implicated prior to conviction and that fourteenth amendment due process concerns were met once the arrestee received adequate medical care. No obligation to pay arises, the Court held, absent a specific state law provision requiring such payment. Because arrestees are subject to physical restraints similar to those imposed on convicted prisoners, this Case Comment argues that courts undertaking to determine the scope of a state's duty to provide treatment to arrestees should apply a due process standard which draws upon eighth amendment analysis. The Comment concludes that under such an eighth amendment equivalence approach, no duty to pay arises because the state's failure to pay the health care provider does not reflect "deliberate indifference" towards the recipient of the treatment.

Delivery of Health Care↗

Cultivation of Schistosoma mansoni in vitro. I. Establishment of cultures from cercariae and development until pairing.

Procedures are described for mass cultivation of Schistosoma mansoni. Cercariae were pooled, concentrated, and axenized through a series of washes in base medium containing antibiotics. Cercariae were sheared through a double-Luer-ended needle connected to two syringes, and tails separated and discarded. Young schistosomules were grown in a medium based upon BME augmented with lactalbumin hydrolysate, glucose, hormones, and other amendments and supplemented with human serum. Human blood cells (Type O) were added to cultures. Intestinal pigment was seen on the 5th day and gut cecal fusion began on day 11. Schistosomules developed steadily to pairing, which was seen first during the 7th wk of culture. Pairing occurred somewhat later in relation to development in vivo.

Animals↗

Sipuleucel-T: APC 8015, APC-8015, prostate cancer vaccine--Dendreon.

Sipuleucel-T [APC 8015, Provenge] is an autologous, dendritic cell-based vaccine under development with Dendreon Corporation for the treatment of androgen-independent and androgen-dependent prostate cancer. It was generated using the company's active immunotherapy platform to stimulate a patient's own immune system to specifically target and destroy cancer cells, while leaving healthy cells unharmed. This approach could provide patients with a meaningful survival benefit and an improved tolerability profile over existing anticancer therapies. Sipuleucel-T selectively targets the prostate-specific antigen (PSA) known as prostatic acid phosphatase (PAP) that is expressed in approximately 95% of prostate cancers. It is produced by ex vivo exposure of dendritic cell precursors to PA 2024, a recombinant fusion protein composed of the PAP target fused to granulocyte-macrophage colony-stimulating factor (GM-CSF) and incorporated into Dendreon's proprietary Antigen Delivery Cassette. Patients are typically administered three intravenous (IV)-infusions of the vaccine over a 1-month period as a complete course of therapy. It is undergoing late-stage clinical evaluation among patients with early and advanced prostate cancer. In November 2003, Kirin Brewery returned to Dendreon the full rights to Sipuleucel-T for Asia. In exchange, Dendreon licensed patent rights relating to the use of certain HLA-DR antibodies to Kirin for $US20 million. This amended agreement enables Dendreon to complete ongoing discussions for a worldwide marketing and sales partnership for Sipuleucel-T. Similarly, Kirin is able to develop its HLA-DR monoclonal antibodies free of potential infringement claims arising from Dendreon's patent rights to HLA-DR. The licensing agreement relates to patent rights owned by Dendreon relating to monoclonal antibodies against the HLA-DR antigen. In addition, Dendreon retains rights to develop and commercialise its two existing HLA-DR monoclonal antibodies, DN 1921 and DN 1924, as well as other HLA-DR antibodies not being developed by Kirin. Previously, in May 1999, Dendreon and Kirin established a collaboration for the development of dendritic cell-based immunotherapeutics for cancer, including Sipuleucel-T. Under the agreement, Kirin would provide financial support for Dendreon's research on dendritic cells focused on developing immunotherapies for cancers most prevalent in Asia. Dendreon would retain US rights to products arising from the collaboration while Kirin would hold the rights to such immuno-therapeutics in Asia and Oceania. In August 2005, Dendreon signed an agreement to lease a commercial manufacturing facility in Hanover, New Jersey, USA. The company intends to develop the facility to meet anticipated clinical and commercial demands of Sipuleucel-T as well as other active immunotherapy product candidates. Dendreon and Diosynth Biotechnology (Akzo Nobel) have an agreement for the commercial production of the PA 2024 antigen component of Sipuleucel-T. In November 2003, Dendreon announced that Diosynth successfully manufactured PA 2024 on a commercial scale. In October 2001, Dendreon announced that Gambro Healthcare Inc. would provide a network of centres for cell collection to support commercial production and clinical development of various Dendreon vaccines, including Sipuleucel-T. Dendreon has outsourced its cell processing operations in Mountain View, California, USA to Progenitor Cell Therapy under an amended agreement signed in August 2002. This agreement is an expansion of an existing agreement, under which Progenitor provided Dendreon with cell-processing services through its facility in Hackensack, New Jersey, USA. The pivotal, two-stage, phase III trial (D9902 study) has been initiated at clinical sites in the US. The first stage of the trial (D9902A study) is a double-blind, placebo-controlled phase III trial designed to evaluate Sipuleucel-T in men with asymptomatic, metastatic, androgen-independent prostate cancer. The trial was originally designed to be the companion study to a previously completed phase III trial, called D9901. However, the D9902A study with 98 patients recruited was halted in December 2002, when analysis of the D9901 study revealed no statistically significant benefit in time to disease progression in the overall group, although a benefit was seen in a subgroup of patients with Gleason scores of < or =7. In April 2002, the US FDA requested clarification regarding cellular composition of Sipuleucel-T and the suspension of additional patient enrollment for the D9902 study; the request was related solely to manufacturing issues without patient safety being an issue. Trial enrollment resumed in October 2002 following FDA authorisation. Dendreon amended the protocol for the D9902 study and is only recruiting patients with asymptomatic, metastatic, androgen-independent prostate cancer, regardless of their Gleason Score (D9902B study). The ongoing pivotal phase III trial underwent a Special Protocol Assessment (SPA) with the FDA in August 2003 and is enrolling approximately 500 patients. The primary endpoint is overall survival with time to objective disease progression being a secondary endpoint. Final 3-year survival analysis of the D9902A study has been completed and presented. Previously, Dendreon completed an earlier phase III trial (D9901 study) that assessed Sipuleucel-T among 127 patients with late-stage, metastatic, hormone-independent prostate cancer in the US. All subjects had undergone surgical resection of the prostate, but had rising levels of PSA. Final 3-year survival data have been reported. Dendreon also conducted a phase II trial, known as D9905, that investigated Sipuleucel-T monotherapy among patients with early-stage prostate cancer. Study findings have been reported. In September 2003, the FDA designated Sipuleucel-T as a fast-track development programme for the treatment of asymptomatic, metastatic, androgen-independent prostate cancer. Subsequently, the FDA granted fast-track status to the vaccine in November 2005. Dendreon announced in September 1999 that a phase I trial of Sipuleucel-T in patients with prostate cancer had commenced in Japan. This study was being conducted at a dendritic cell processing centre that was formed as part of Dendreon's collaboration with Kirin. In addition, the US NCI is conducting a phase II trial (P-16) of Sipuleucel-T in combination with bevacizumab among patients with hormone-dependent prostate cancer. Trial results have been announced. In April 2001, Dendreon was awarded a US patent (No. 6,210,662) covering the composition of Sipuleucel-T. Dendreon acquired an exclusive worldwide licence to dendritic cell therapy for cancers and other diseases from the Immune Response Corporation; Immune Response originally received the exclusive patent rights to the technology from the University of Brussels in Belgium.

Cancer Vaccines↗

Morphology of the deep-sea copepod Bobkabata kabatabobbus (Lernaeosoleidae: Poecilostomatoida) and amended diagnosis of Lernaeosoleidae.

New morphological information on the deep-sea parasitic copepod Bobkabata kabatabobbus Hogans and Benz, 1990 (Lernaeosoleidae: Poecilostomatoida) is provided based on 2 newly discovered, complete specimens collected from a pallid sculpin, Cottunculus thomsoni (Gunther, 1882), captured in water 1,463 m deep in Welker Canyon off Rhode Island (western North Atlantic). The first antennae of both specimens were tiny, indistinctly segmented, and armed with spiniform setae. Terminal segments of the second antennae were robust hooks and were impossible to disengage from the host without severing them from their basal sockets. A simple orifice without any associated appendages may have represented the mouth. Both specimens were transformed adult females and each was embedded in the flesh of their scaleless host up to where the pregenital trunk began to broaden into its characteristic horseshoe shape. Whereas each copepod's bulbous cephalothorax appeared to be the primary attachment device, the powerfully hooked second antennae seemed positioned to facilitate the application of the presumed mouth to the host. A revised family diagnosis for Lernaeosoleidae Hogans and Benz, 1990 is provided that primarily differentiates Lernaeosoleidae from the closely allied Chondracanthidae H. Milne-Edwards, 1840 and other poecilostomatoids based on the absence of mandibles, first and second maxillae, maxillipeds, and thoracic legs 1-4 in lernaeosoleids.

Animals↗

Biodegradation of cyclodextrins in soil.

Cyclodextrins, especially random methylated betaCD (RAMEB) and hydroxypropyl betaCD (HPbetaCD), are becoming common enhancing additives in the bioremediation of soils formerly contaminated by hydrocarbons and/or other poorly bioavailable organic pollutants. Therefore, their degradation in the soil, particularly the most persistent RAMEB, has been of great concern. Like oil contaminants, these additives should be biodegradable via an environmentally safe technology. Hence, in this paper, the biodegradability of eight different cyclodextrins (CDs) in four different soils was examined under various treatment conditions in laboratory and pilot scale field experiments. This paper is the first report on the potential biological fate of CDs studied under a large variety of environmental conditions and in different soil ecosystems. Data on the potential relationship between CD biodegradation and the biological removal of hydrocarbons in the CD-amended contaminated soils are also given. All CDs were found to be more or less biodegradable; even the most persistent RAMEB was depleted from soils under favourable conditions. In the field experiments, the depletion of RAMEB to about 40% of its initial level was observed for a period of 2 years in hydrocarbon-contaminated soils of high organic matter and cell concentration.

Acetylation↗

The effects of soil amendments on heavy metal bioavailability in two contaminated Mediterranean soils.

Two heavy metal contaminated calcareous soils from the Mediterranean region of Spain were studied. One soil, from the province of Murcia, was characterised by very high total levels of Pb (1572 mg kg(-1)) and Zn (2602 mg kg(-1)), whilst the second, from Valencia, had elevated concentrations of Cu (72 mg kg(-1)) and Pb (190 mg kg(-1)). The effects of two contrasting organic amendments (fresh manure and mature compost) and the chelate ethylenediaminetetraacetic acid (EDTA) on soil fractionation of Cu, Fe, Mn, Pb and Zn, their uptake by plants and plant growth were determined. For Murcia soil, Brassica juncea (L.) Czern. was grown first, followed by radish (Raphanus sativus L.). For Valencia soil, Beta maritima L. was followed by radish. Bioavailability of metals was expressed in terms of concentrations extractable with 0.1 M CaCl2 or diethylenetriaminepentaacetic acid (DTPA). In the Murcia soil, heavy metal bioavailability was decreased more greatly by manure than by the highly-humified compost. EDTA (2 mmol kg(-1) soil) had only a limited effect on metal uptake by plants. The metal-solubilising effect of EDTA was shorter-lived in the less contaminated, more highly calcareous Valencia soil. When correlation coefficients were calculated for plant tissue and bioavailable metals, the clearest relationships were for Beta maritima and radish.

Animals↗

OSHA's renewed mandate for regulatory flexibility review: in support of the 1984 ethylene oxide standard.

BACKGROUND: The Regulatory Flexibility Act of 1980 requires that all federal agencies consider the impact of regulations on small entities. One of the provisions of the Act requires review of regulations ever 10 years to determine whether such regulations should be continued without changes, rescinded, or amended to make them more effective or less burdensome on businesses. The Small Business Regulatory Enforcement Fairness Act (SBREFA) of 1996 amended and expanded the Regulatory Flexibility Act. Most significantly, SBREFA entitles aggrieved small entities or their representative (e.g., trade associations) to sue OSHA for failure to fulfill Regulatory Flexibility Act requirements. In response to this new political reality, OSHA held the first public meeting of their kind in June of 1997 to gather information on the ethylene oxide and lock-out/tag-out standards for the purposes of Regulatory Flexibility review. METHOD: This paper presents the development of the Regulatory Flexibility review process and details our analysis of the ethylene oxide standard using OSHA's eight Regulatory Flexibility review criteria. RESULTS: Great progress in ethylene oxide health and safety has been made since the promulgation of the standard in 1984, including a considerable decrease in average workshift exposures. Yet, important concerns remain, such as the lack of safer substitutes for EtO's most common uses, the widespread occurrence of accidental exposures to EtO that are not captured by personal monitoring, and the recent increase in the occurrence of catastrophic EtO explosions. CONCLUSIONS: Because of the considerable study that has been devoted to EtO and to the EtO standard, there is a very strong cases for either making the EtO standard more worker protective, or continuing the standard without change while improving outreach and enforcement efforts to address shortcomings. Other valuable standards for which fewer data exist may be inappropriately threatened by the Regulatory Flexibility review process. Importantly, Regulatory Flexibility review could be constructive if accompanied by appropriations to fund sound evaluation studies. Instead, it will likely divert OSHA's limited resources from the numerous urgent health hazard that await initial rule-making. As signified by the designation of "intervention effectiveness research" as one of the 21 priorities on the National Occupational Research Agenda, evaluation studies of OSHA standards and other interventions are urgently needed. The occupational health community's response to this need will play a crucial role in preserving hard-won protections, as well as in developing other urgently needed protections in the future.

Environmental Monitoring↗

Cysteine-mediated reductive dissolution of poorly crystalline iron(III) oxides by Geobacter sulfurreducens.

The reductive dissolution of poorly crystalline ferric oxides in the presence of cysteine was investigated to evaluate the potential of cysteine as a possible electron carrier to stimulate the reduction of iron(III) oxides by Geobacter sulfurreducens. The extent and rate of biotic and abiotic reduction of iron(III) oxides in the presence of cysteine at various concentrations were compared. Iron(III) oxides were reduced abiotically by cysteine. The initial rate and extent of iron(III) oxide reduction were correlated linearly with the cysteine concentration ranging from 0 to 6 mM. Also, addition of 0.5-2 mM cysteine significantly stimulated the rate and the extent of iron(III) oxide reduction in cultures of G. sulfurreducens. The cysteine concentration decreased in accordance with the increase of Fe(II) concentration and reached a nearly constant residual concentration. Cysteine depletion followed first-order kinetics and increased linearly with the cysteine concentration. An 8- to 11-fold increase in the extent of iron(III) oxide reduction relative to the abiotic system was observed. Comparison of sorbed and dissolved Fe(II) concentrations between cultures amended with cysteine and with other organic chelators showed that solubilization is not the main factor in cysteine-stimulated Fe(III) reduction. Addition of cystine could enhanced the extent of iron(III) oxide reduction, concomitant with the increase of the regenerated cysteine concentration and support the hypothesis that cysteine could serve as an electron carrier to transfer electrons from G. sulfurreducens to poorly crystalline iron(III) oxides.

Adsorption↗

Administrative issues involved in disaster management in India.

India as a country is vulnerable to a number of disasters, from earthquakes to floods. Poor and weaker members of the society have always been more vulnerable to various types of disasters. Disasters result in unacceptably high morbidity and mortality amongst the affected population. Damage to infrastructure and reduction in revenues from the affected region due to low yield add to the economic losses. Poor co-ordination at the local level, lack of early-warning systems, often very slow responses, paucity of trained dedicated clinicians, lack of search and rescue facilities and poor community empowerment are some of the factors, which have been contributing to poor response following disasters in the past. The first formal step towards development of policies relating to disaster care in India was the formulation of the National Disaster Response Plan (NDRP) which was formulated initially by the Government of India for managing natural disasters only. However, this was subsequently amended to include man-made disasters as well. It sets the scene for formulating state and district level plans in all states to bring cohesiveness and a degree of uniform management in dealing with disasters. A National Disaster Management Authority has been constituted which aims to provide national guidelines and is headed by the Prime Minister of India. It is the highest decision-making body for the management of disasters in the country. The authority has the responsibility for co-ordinating response and post-disaster relief and rehabilitation. Each state is required to set up Disaster Management Authorities and District Disaster Management Committees for co-ordination and close supervision of activities and efforts related to the management of disasters.

Disaster Planning↗

Phase I and pharmacokinetic study of irinotecan administered as a low-dose, continuous intravenous infusion over 14 days in patients with malignant solid tumors.

PURPOSE: To evaluate the feasibility of administering irinotecan as a continuous intravenous infusion for 14 to 21 days. PATIENTS AND METHODS: Patients with solid tumors refractory to standard therapy received continuous infusions of irinotecan by means of an ambulatory infusion pump. The starting dosage was 12.5 mg/m(2)/d for 14 days every 3 weeks. After identification of the maximum-tolerated dose for the 14-day infusion schedule, the protocol was amended to prolong the infusion duration to 17 and 21 days. Pharmacokinetics of irinotecan and SN-38 and its glucuronide were determined using high-performance liquid chromatography and noncompartmental modeling. RESULTS: Thirty-three patients received 85+ courses. At the first dose level (12.5 mg/m(2)/d), cumulative grade 3 or 4 diarrhea and grade 3 or 4 neutropenia occurred in three of five patients. At a dosage of 10 mg/m(2)/d, 14-day administration resulted in grade 4 diarrhea in two of six patients and one episode of grade 4 vomiting occurred, whereas with 17-day administration, one episode of grade 3 nausea and two episodes of grade 3 or 4 diarrhea were observed in six patients. Increasing the number of days of infusion to 21 days was not feasible because of cumulative diarrhea. Hematologic toxicity was rare. The mean metabolic SN-38 area under the curve/irinotecan area under the curve ratio was 16% +/- 6% compared with 3% to 5% after short infusion schedules involving therapeutic dosages. Partial responses were observed in two patients with extraovarian and colorectal cancer. CONCLUSION: The recommended dosage is 10 mg/m(2)/d for 14 days, repeated every 3 weeks. Enhanced metabolism of irinotecan to SN-38 may explain in part the low recommended dose for this schedule.

Adult↗

A microcomputer system for prescription, calculation, verification and recording of radiotherapy treatments.

The design of a microcomputer system for the reduction of mistakes in radiotherapy is described. The system covers prescription entry, prescription and treatment calculations, and verification and recording of the treatment set-up. A telecobalt unit was interfaced to the system and in the first 12 months 400 patients have been prescribed and 5000 treatment fields verified. The prescription is entered by the medical officer using an interactive program and this prescription provides the reference for verifying the treatment set-up. The program allows amendments to the prescription to be made easily during the treatment course. The treatment parameters verified are field size, wedge and treatment time. The system uses bar-codes for patient and field identification. A reduction in the number of mistakes has been achieved and future developments are discussed.

Computers↗