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PubMed1991

The epidemiological future.

Forecasting the epidemiological future of industrialized countries for about thirty or maybe fifty years has been attempted. This will be determined by the future condition of relevant factors of the physical-biological, socio-economic and cultural environment of the population in question and by the socio-demographic structures of the population itself. It is highly probable that substantial development in prevention and curing of diseases, and in a few cases even breakthroughs will occur in the next three decades or so. Also public awareness with respect to health promotion can be expected to rise substantially in the future. Under these circumstances health conscious behaviour and sophisticated medical technology will have a much more serious impact on the health of the population in the future than at present. The aging of the population will become faster as fertility is expected to remain constant at very low levels and mortality will become the major cause of aging. Consequently general mortality will eventually increase, yet infant mortality will further decrease and will be as low as 6.0 per thousand live births by the 2020's. Lifespan prolongation by selective dietary restrictions would become a feasible human option. If some chronic degenerative diseases will be eliminated or will be put at least under control then life expectancy at birth can be as high as 84.3 years. However, it has been suggested that delaying the progression of chronic diseases is more realistic than eliminating them. Consequently the prevalence of chronic disease in the population will increase, along with the associated costs of treatment and care. Yet another school of thinking forecasts the 'compression of morbidity'. It is an open question whether inequalities in health will increase or decrease. AIDS infection will spread dramatically, but mainly in the third world and prevention strategies will use general information, education and counselling in order to increase public awareness with respect to the chances of avoiding infection.

Chronic Disease↗
PubMed2002

Role of macropore continuity and tortuosity on solute transport in soils: 2. Interactions with model assumptions for macropore description.

The impact of macropore description on solute transport predictions in soils is not well understood. A 2-D Galerkin finite element model was used to compare different approaches for describing macropore flow in soil. The approaches were: a modification of the hydraulic conductivity function (Hydraulic function), the lumping of all macropores into one single straight macropore (Lumping), the use of an exchange factor between microporosities and macroporosities that occupy the same area (Dual porosity), and a detailed description of each macropore (Full description, base case). Simulated breakthrough curves were obtained with domains that contained one or more macropores of different shapes under both steady state and transient flow conditions. The Hydraulic function approach was not sensitive to macropore continuity and tortuosity. When the macropores were open at the soil surface and the solute was surface applied, the first three approaches underestimated both breakthrough curves and solute distribution in the profile compared to the Full description approach. When the solute was initially incorporated in the soil, the first three approaches overestimated the breakthrough curves compared to the Full description approach. The first three approaches also underestimated the heterogeneity of solute distribution in the profile compared to the Full description approach, mostly when the macropores were tortuous. The differences between predicted breakthrough curves with different approaches decreased with an increase in tortuosity and a decrease in surface continuity. To simplify macropore description, the Dual porosity approach was the better of the first three approaches for predicting breakthrough curves provided the exchange factor between macropores and matrix porosity was available.

Diffusion↗
PubMed2001

No-anesthesia clear corneal phacoemulsification versus topical and topical plus intracameral anesthesia. Randomized clinical trial.

PURPOSE: To compare the intraoperative pain scores during clear corneal phacoemulsification under no anesthesia, topical anesthesia, and topical plus intracameral anesthesia. SETTING: Dr. Agarwal's Eye Hospital and Eye Research Center, Chennai, India. METHODS: Seventy-five patients were randomized to have phacoemulsification under no anesthesia, topical anesthesia, or topical plus intracameral anesthesia. Uncooperative or illiterate patients and those with hard cataract, a shallow anterior chamber, or small pupils were excluded. A protocol was established for supplemental anesthesia in case of breakthrough pain during the surgery. Each patient was asked to grade the overall severity of intraoperative pain immediately after surgery on a 10-point visual analog scale. Also evaluated were the general discomfort during surgery, discomfort from the microscope lights, surgeon stress during surgery, and total surgical time. Comparison among the 3 groups was performed using an analysis of variance. RESULTS: No supplemental anesthesia was required in any group. No significant difference was noted in the mean scores of the subjective sensation of pain with or without topical anesthesia (P =.610). The mean scores of patient discomfort from the microscope lights and surgical time were also statistically insignificant. Patient discomfort and surgeon stress during surgery were significantly greater in the no-anesthesia group than in the topical and topical plus intracameral groups (P =.0235 and P = 0.0206, respectively). CONCLUSION: No-anesthesia clear corneal phacoemulsification was performed by a highly experienced, skilled surgeon without causing an unacceptable level of pain. However, this technique is not suitable for every cataract surgeon or patient.

Adult↗
PubMed1998

The effect of chemoprophylaxis on the timing of onset of falciparum malaria.

The association between chemoprophylaxis and delayed onset of falciparum malaria was investigated in a retrospective study of 477 nonimmune cases reported to the UK Malaria Reference Laboratory (MRL) who had used either mefloquine (n = 56), chloroquine-proguanil (n = 90) or no chemoprophylaxis (n = 331). For holiday and short-term travellers using mefloquine the time between arrival in the UK and diagnosis was found to be significantly longer than for chloroquine and proguanil (C-P) users or for those who had not used prophylaxis at all (P < 0.004). This delay was primarily due to a later onset of symptoms. C-P use was not associated with delay in onset of symptoms or diagnosis when compared to not using prophylaxis. Possible reasons for the findings are discussed. Mefloquine may continue to exert a partially suppressive effect on resistant strains of Plasmodium falciparum (Pf). That chloroquine with proguanil was not found to have such an effect may be due to poor compliance to proguanil or differences in the mode of action and range of parasite resistance to the two regimens. Differences in drug compliance may be one reason why only mefloquine users on holiday or short-term journeys experienced delays to onset of disease. Drug compliance amongst cases of breakthrough malaria on chemoprophylaxis may be lower than is generally recognized. It is important for clinicians and travellers to be aware that the onset of falciparum malaria may be delayed by mefloquine prophylaxis.

Antimalarials↗
PubMed1974

Three flies and three islands: parallel evolution in Drosophila.

Most organisms are evolutionary conservatives; they may subdivide their niches but tend to remain within them. Yet the fossil record shows many cases of breakthrough to a new mode of life. How may such evolutionary innovation be recognized at this time level? Three species of Drosophila have accomplished an innovation in that they breed as obligate commensals on tropical land crabs. This could be dismissed as a curious aberration were it not for the fact that the three flies concerned represent three different phyletic lines of the family. Although Drosophila is abundant on the continents, these three parallel innovative evolutions have occurred on islands. The proposal is made that the genetic systems of many conservative groups of organisms carry variability that would permit them to evolve in a novel direction. The realization of this capacity, however, is possible only under special environmental conditions.

Adaptation, Biological↗
PubMed2003

Contextualizing a medical breakthrough: an overview of the case of IVF.

In this article I examine the ways in which the technology of in vitro fertilization (IVF) is embedded in prevailing sociocultural perceptions and power relations in North American and Western European contexts. From this perspective, I look at the efforts involved in developing reproductive technologies and at the particular direction such attempts have taken. I then examine the policies and laws through which IVF is regulated; the technical characteristics of the technology and its implementation; the social implications of IVF for poorer women, women of color, and single and lesbian women; and the media coverage of the subject. Women's responses to IVF and their roles in its shaping are also addressed. I conclude with a reference to the social and cultural repercussions of IVF in the industrialized world. The overview suggests that IVF embodies social continuity while also encapsulating a potential for radical social transformations.

Attitude to Health↗
PubMedDate not supplied

Tissue engineering: the end of the beginning.

This study was undertaken to assess the impact of current economic conditions and recent disappointing product launches on the field of tissue engineering. Data were collected on all firms known to be active in the field, analyzed, and compared with analogous data collected in 1995, 1998, and 2000. As of December 31, 2002, more than 2600 full-time equivalents (FTEs) in 15 countries and 89 firms were engaged in tissue-engineering research and development. Annual spending was US dollars 487 million, down about 20% since 2000-a reasonable performance in the face of a stagnant economy and difficult capital markets. Individual sectors proved far more volatile. Activity in skin, cartilage, and other structural applications declined by more than 50% with a loss of 800 FTEs. This downsizing was somewhat counterbalanced by a 42% increase in stem cell firms, which added more than 300 employees. Consistent with general disenchantment with technology sector equities, capital value of publicly traded tissue-engineering corporations has decreased by almost 90% from US dollars 2.5 billion at the end of 2000 to US dollars 300 million at the end of 2002. The United States' fraction of the total workforce declined from 80% in 2000 to 54% in 2002. By the close of 2002, twenty tissue-engineered products had entered Food and Drug Administration clinical trials. Four were approved but none of these are yet commercially successful. Six other applications were either abandoned or failed to achieve product approval. Ten products were still in clinical trials, some of which were investigator sponsored, and most of which were at the phase I/phase II stage. The field has yet to produce a profitable product despite an aggregate research and development investment exceeding US dollars 4.5 billion. Tissue engineering is clearly having difficulty transitioning from a development stage industry to one with a successful product portfolio. This is often the case for breakthrough medical technologies.

Clinical Trials as Topic↗
PubMed2003

Incidence of new renal parenchymal inflammatory changes following breakthrough urinary tract infection in patients with vesicoureteral reflux treated with antibiotic prophylaxis: evaluation by 99MTechnetium dimercapto-succinic acid renal scan.

PURPOSE: Breakthrough urinary tract infections (UTI) are considered an indication for surgical intervention in children with vesicoureteral reflux (VUR) with the goal of preventing new or progressive renal scarring. We assessed the incidence of new renal parenchymal inflammatory changes following breakthrough UTI in patients on antibiotic prophylaxis for VUR. MATERIALS AND METHODS: We prospectively analyzed 38 patients (62 refluxing renal units) with VUR. All patients experienced a culture documented breakthrough UTI (greater than 100,000 cfu/ml) while taking antibiotic prophylaxis. Dimercapto-succinic acid (DMSA) scans were obtained 4 to 6 weeks after UTI to detect new renal inflammatory changes and all scans were reviewed by the same pediatric nuclear medicine specialist (MM). To avoid misinterpretation of preexistent renal scarring for acute inflammation, new pyelonephritis was confirmed by comparison to prior DMSA scan. RESULTS: Of 38 patients 14 (38%) had preexistent renal scarring but only 1 (7%) manifested new changes on DMSA scan. Of the remaining 24 patients with normal baseline studies 3 (12.5%) had changes after UTI. Overall, only 4 patients (10.5%) manifested new changes on DMSA scan. Three additional patients who did not have a baseline scan for comparison demonstrated unequivocal changes of acute pyelonephritis on DMSA scan, increasing the incidence to 17% (7 of 41). Of the patients 7 (17%) underwent surgical correction of reflux and 34 (83%) were maintained on antibiotic prophylaxis. CONCLUSIONS: Of patients with VUR who experienced a single breakthrough UTI while on antibiotic prophylaxis, at most only 17% had renal inflammatory changes on acute DMSA scan. Our findings endorse the usefulness of DMSA scan in tailoring management of VUR and breakthrough UTI cases, and lend support to continued nonoperative management for the majority.

Antibiotic Prophylaxis↗
PubMedDate not supplied

Vesicoureteral reflux: diagnosis and management.

Vesicoureteral reflux is the retrograde passage of urine from the bladder into the ureter and kidneys during voiding. This commonly-treated entity is frequently managed by different disciplines that include Urology, Nephrology and Pediatrics. The pathophysiology of vesicoureteral reflux seems to be related to the valve mechanism of the ureterovesical junction. Abnormal location of the ureteral orifice is implicated in the short ureteral tunnel which in turn compromised the flap-valve mechanism. The grading of reflux is important since management depends on the severity according to a five grade system. At present, medical management using antibiotic prophylaxis has become well established for managing patients with low-grade reflux (grades I-III). Moderate reflux (grade III-IV) could be managed by surgery in case of breakthrough infections. Recommendations regarding the diagnosis and medical management remain complex and are continuously evolving. More frequently than not, treating pediatricians and urologists would have to make decisions by individualizing each patient and considering the likelihood that patient's reflux will resolve.

Anti-Infective Agents, Urinary↗
PubMed1986

Live attenuated varicella vaccine use in immunocompromised children and adults.

Live attenuated varicella vaccine has been administered to 307 children with leukemia in remission and to 86 healthy adults. The vaccine was well tolerated and immunogenic. The major side effect in leukemic children receiving maintenance chemotherapy was development of a vaccine-associated rash. Vaccinees in whom a rash developed were potentially somewhat infectious to others about 1 month after immunization. Vaccination was not associated with an increase in the incidence of herpes zoster or in relapse of leukemia. Vaccination provided excellent protection against severe varicella. It was associated with a significant decrease in the attack rate of chickenpox following an intimate exposure to varicella-zoster virus, conferring about 80% protection in leukemic children. The cases of breakthrough varicella that occurred were mild. Thus, the vaccine may either prevent or modify varicella in high-risk individuals. It may also have use for prevention of nosocomial varicella.

Adult↗
PubMed1992

Six-year follow-up study on the efficacy and safety of vigabatrin in patients with epilepsy.

Twenty-five patients with epilepsy (mostly with partial seizures) who had responded favourably to a short-term trial of add-on vigabatrin entered maintenance treatment. After 52 to 78 months, 15 patients continue to take the drug with good therapeutic response. Median monthly seizure frequency during the last 2 months on vigabatrin in all patients, including drop-outs, was 3.5 (range 0-74) as compared with 10 (range 3-98) during an initial placebo period (p < 0.01). Drop-outs were caused by adverse events in 2 cases (ataxia and psychotic symptoms respectively), seizure breakthrough in 4 cases and reasons unrelated to treatment in 4 patients. In most patients, side effects were absent or mild, the most frequent complaint being weight gain. It is concluded that the antiepileptic efficacy and good clinical tolerability of vigabatrin are generally maintained during long-term treatment for up to 6 years.

Adolescent↗
PubMed2004

Managing breakthrough pain: a clinical review with three case studies using oral transmucosal fentanyl citrate.

Pain management begins with the use of appropriate assessment tools and includes planning, implementing, and evaluating a comprehensive treatment plan that addresses persistent and breakthrough pain. Persistent pain is present to some degree throughout the day and primarily is controlled with around-the-clock medication. However, it often is accompanied by episodes of short, intermittent pain, also known as breakthrough pain. From a clinical perspective, breakthrough pain is characterized as a transitory exacerbation of pain that occurs on a background of otherwise stable pain in a patient receiving chronic opioid therapy. Breakthrough pain typically is moderate to severe in intensity and can be triggered by various activities (incident pain), be entirely unpredictable (idiopathic pain), or occur toward the end of around-the-clock medication (end-of-dose failure). Breakthrough pain occurs in as many as 86% of patients with cancer even when persistent pain is well controlled. Clinicians and patients should address persistent and breakthrough pain as distinct entities to accurately assess it and develop appropriate pain management plans. This article provides an overview of the clinical characteristics of persistent and breakthrough pain and, through the use of three case studies, illustrates practical strategies for managing breakthrough pain effectively.

Administration, Buccal↗
PubMed1981

Malaria 'breakthroughs' and resistance to chloroquine in Africa. Case reports.

Four cases of Plasmodium falciparum malaria are presented. These cases are typical of chloroquine resistant malaria, with their pattern of 'breakthrough' malaria despite chloroquine prophylaxis, absence of response to therapeutic doses of chloroquine and recrudescence of the malarial parasites. These cases should alert physicians in other parts of the world, who may have to treat travelers from Central and West Africa, and particularly from the Ivory Coast, to the possibility that the malaria contracted in these areas may be chloroquine-resistant. The most effective drug in these cases appears to be a combination of sulphadoxine and pyrimethamine.

Adolescent↗
PubMed1990

The long-term postoperative trinitroglycerin hypotension in normal perfusion pressure breakthrough syndrome.

The authors describe a case of normal perfusion pressure breakthrough syndrome, a catastrophic hemorrhage complicating surgery for cerebral arteriovenous malformations, due to chronic loss of autoregulation. Successful treatment was achieved with prolonged postoperative trinitroglycerin hypotension, associated with barbiturate-induced coma and artificial ventilation.

Journal Article↗
PubMed2002

Course of virologic breakthroughs under long-term lamivudine in HBeAg-negative precore mutant HBV liver disease.

We studied the course of virologic breakthroughs detected by a quantitative polymerase chain reaction (PCR) assay in 32 of 78 patients with hepatitis B e antigen (HBeAg)-negative precore mutant hepatitis B virus (HBV) chronic liver disease under long-term lamivudine monotherapy. Serum HBV DNA levels were measured every 3 months and on every biochemical breakthrough. YMDD mutants were detected in 30 of the 32 patients with virologic breakthroughs. Among these 32 patients, biochemical remission rate was 44% at 6 months, 21% at 12 months, and 0% at 24 months after the onset of virologic breakthrough. Development of biochemical breakthroughs was associated with a significant increase of serum HBV DNA levels, which exceeded 100,000 copies/mL in 19 of 20 patients (95%) with biochemical breakthroughs and in only 1 of 8 patients (12.5%) remaining in biochemical remission for at least 6 months after the onset of virologic breakthrough (P <.001). Alanine aminotransferase (ALT) level peaked within 0 to 3 months after the onset of biochemical breakthrough and decreased at 6 months but remained abnormal in all but 2 patients. Follow-up liver histologic lesions in patients with biochemical breakthroughs did not differ from baseline findings, although they were significantly improved in patients remaining in virologic and biochemical remission. In conclusion, the frequent emergence of viral resistance under long-term lamivudine monotherapy in HBeAg-negative precore mutant HBV chronic liver disease is followed by increasing viremia levels culminating in the development of biochemical breakthroughs in most cases. ALT activity peaks close to the onset of biochemical breakthrough, decreasing thereafter but remaining persistently abnormal with fluctuating levels.

Adult↗
PubMed1999

Adsorption properties and breakthrough model of 1,1-dichloro-1-fluoroethane on activated carbons.

Hydrochlorofluorocarbons (HCFCs), among the major replacements for chlorofluorocarbons (CFCs) and chlorinated solvents, are now considered to the prime contribution to the stratospheric ozone depletion. This paper reports the adsorption equilibrium of 1,1-dichloro-1-fluoroethane (HCFC-141b) vapor in air streams on the commercial activated carbons PCB and BPL, which were made from coconut shell and bituminous coal, respectively, at 283, 293, 303, and 313 K. The experimental results show that within the experimental conditions, the adsorption capacities of the two adsorbents for HCFC-141b in dry air streams can be well-fitted by the Langmuir, Freundlich, and Dubinin-Radushkevich (D-R) adsorption equations. The physical properties of the adsorbents are consistent with the isotherm parameters obtained from the adsorption results. In addition, available experimental data of adsorption breakthrough at 283 K were used in conjunction with the Yoon and Nelson model to generate theoretical breakthrough curves based on the obtained values of parameters. In each case, calculated theoretical breakthrough curves are in agreement with corresponding experimental data.

Journal Article↗
PubMed1985

Chromosomal abnormalities in the Kaiser-Permanente Birth Defects Study, with special reference to contraceptive use around the time of conception.

Chromosomal abnormalities were studied in 33,551 abortions and births to women whose contraceptive histories had been recorded at their first antenatal visit in 1975-1977. Chromosome examinations were performed exclusively on clinical grounds. There were 45 de novo abnormalities detected (1.34/1,000); three of them were detected at amniocentesis. Trisomy 21 was observed in 27 cases (0.80/1,000), trisomy 18 in nine (0.27), other trisomies in three (0.09), and translocations or deletions in five (0.15). One case of triploidy and six cases of inherited abnormalities were detected. There were no significant racial variations. No increase in risk for chromosomal abnormalities was found among women who had used oral contraceptives prior to becoming pregnant or among women who experienced oral contraceptive breakthrough pregnancies. Two cases of trisomy 18 were observed among the 814 deliveries following oral contraceptive breakthrough conceptions (2.46/1,000), two cases of trisomy 21 occurred in 338 births following failures of rhythm contraception (5.92/1,000), and no cases of trisomy 21 or 18 among the 1,569 women using spermicides at the time of conception.

Abnormalities, Drug-Induced↗
PubMed1990

Contaminant breakthrough: a theoretical study of charcoal sampling tubes.

A previously developed theoretical model was applied to investigate contaminant breakthrough on charcoal sampling tubes. Associated with the model are two important theoretical parameters. These parameters are k' (a rate constant) and tau (the time required for 50% contaminant breakthrough). In this study, values of K' and tau were determined for n-heptane at five different concentration levels in air: 98, 117, 234, 330, and 988 ppm. These values were used along with pertinent theoretical considerations to calculate the entire (0-100%) breakthrough curve (plot of percent breakthrough versus time) regarding the adsorbance of n-heptane on charcoal sampling tubes. In addition, available experimental data for perchloroethylene, isobutyl acetate, ethyl acetate, and dichloromethane were used in conjunction with the theory to generate theoretical breakthrough curves over the entire range of 0 to 100%. In each case, calculated theoretical breakthrough curves are in remarkable agreement with corresponding experimental data. With the use of an additional theoretical parameter, a, the theory was extended to calculate the weight of contaminant collected on a single element (section) of a charcoal sampling tube at 10% breakthrough and at each of several different contaminant assault concentrations.

Acetates↗