The Stiff Joint: Comparative Evaluation of Monotherapy and Combination Therapy With Urate Lowering Agents in Managing Acute Gout.

Gout, an extremely painful form of arthritis, is triggered by the innate immune system's response to the accumulation of monosodium urate crystals in specific joints and surrounding tissues. This condition is characterized by recurring episodes of excruciating arthritis flares, interspersed with periods of disease quiescence. Over time, gout can result in disability, tophi formation, and severe pain. The treatment of gout is centered around two main objectives: alleviating inflammation and pain during acute gout attacks and long-term management to reduce serum urate levels and mitigate the risk of future attacks. Addressing inflammation and pain during acute attacks is often complicated by various factors, including underlying health conditions commonly associated with gout, such as hypertension, chronic kidney disease, cardiovascular disease, and diabetes mellitus. Moreover, gout patients are frequently older and have multiple coexisting health issues, necessitating complex medication regimens. Given the rising prevalence of gout and its associated comorbidities, there's a growing demand for improved treatment options. While existing treatments effectively manage gout in some patients, a significant portion, particularly those with comorbidities, face contraindications to these treatments and require alternative approaches. Innovative medications are required to enhance gout treatment, especially for individuals with concurrent health conditions. These considerations underscore the importance of reviewing both monotherapy and combination therapy approaches for acute gout treatment.

[Perioperative risk assessment of geriatric patients undergoing noncardiac surgery]. / Perioperative Risikostratifizierung geriatrischer Patienten bei nichtkardialen Eingriffen.

BACKGROUND: Older patients more often suffer perioperative complications than younger people. Especially geriatric patients who require emergency treatment represent a high-risk group. Therefore, perioperative risk assessment supports the treatment team in identifying patients at risk and in defining the treatment plan accordingly. MATERIALS AND METHODS: A thorough medical history and clinical examination are pivotal elements of any risk stratification. The organ-specific risk assessment is primarily used to plan the surgical and anesthesiological procedures. RESULTS: For a comprehensive risk assessment in geriatric patients, the organ-specific risk stratification is insufficient. Assessment instruments that reflect the idiosyncrasies of multidimensional disease in geriatric patients can complement risk stratification. These should include the assessment of multimorbidity, frailty, nutrition, activities of daily living, and cognition. In addition to risk prediction, geriatric assessment has the major advantage of providing both a diagnostic and a planning perspective. This allows the implementation of supporting measures for optimal perioperative care, which is the goal of any risk stratification. Risk scores provide a global assessment, but they have their limitations in predicting individual patient risk.

On the genetic background of the adaptive response to X-rays in Drosophila melanogaster.

The effects of a low dose (0.1-20 mGy) preirradiation with X-rays followed by a higher dose (2 Gy) of the same radiation on the recovery of the genetic damage induced as dominant lethals in mature oocytes (stage 14) of different strains of Drosophila melanogaster were investigated. The response was shown to be dependent on the genotype of the flies tested, since lower frequencies of dominant lethals (DL) were only obtained in strains carrying the white mutation. Based on these observations experiments to locate the genetic factor responsible for the adaptive response (AR) were performed. This factor was found to be in a specific region of the X-chromosome. Additional experiments were carried out to give information on the minimal dose required to induce the AR. The results showed that the lowest dose needed is 0.2 mGy. Increasing the conditioning X-ray dose had no influence on the response.

Cytogenetic findings in echographically defined blighted ovum abortions.

A sample of 52 spontaneous blighted ovum abortions (BO) was examined cytogenetically and compared with a sample of abortions with echographic evidence of the embryo (AE). Abnormal karyotypes were 67% in the BO sample and 53% in the AE sample, a non significant difference. In the BO abortions trisomies were 74% of the abnormal karyotypes but 35% in the AE abortion, and the 45,X karyotype was absent among the BO but was found in 10 cases of AE. The prevalence of trisomies 16 and 22 in the BO abortions indicates that genes on these chromosome may be responsible for the early arrest of embryonic development.

Qualitatively different induction of germ cell mutations by heavy ions. A dual target theory.

The problem of the dependence of the biological efficiency of ionizing radiation on the Linear Energy Transfer (LET) is still unsolved. Unexpected reactions of heavy ion irradiated cellular systems such as an increasing Relative Biological Effectiveness (RBE) up to a LET of about 100 keV/micron and then a decrease below 1 oblige to dismiss some conventional interpretations. Several years ago we suggested that, especially by higher ionization density in addition to the DNA, repair systems and (or) membraneous systems could also be injured (dual target theory). Our experiments with heavy ions at the Lawrence Berkeley Laboratory with LET's between 102-970 keV/micron on different types of mutations show a strict distinction between events connected with fusion modalities (repair or misrepair) and those associated with nonfusion. With very high LET misrepair reactions such as translocations disappear, suggesting the direct damage of the repair systems and confirming our previous experiments with peak pions and ions of LET's between 1100-4800 keV/micron.

Oxygen-effect as an inhibition of repair: radiation studies on excision repair deficient mei-9L1-embryos of Drosophila.

The excision repair deficient mei-9L1-embryos of Drosophila melanogaster are up to four times more radiosensitive than normal +/+ embryos. The lack of oxygen-effect in the repair deficient 4-h-embryos and the reduced O2-effect in the 13/4-h embryos suggest an interpretation of the oxygen effect as a modification of the ability to repair. The conversion of the early death (heavy damage) to late death (slight damage) by irradiation of normal embryos in N2 supports this interpretation. This theory can also explain the dependence of O2-effect on LET. The spontaneous lethality and the increase in radiosensitivity depend in heterozygous mei-9L1-embryos strictly upon the genotype of the mother, thus representing a maternal effect.