Ciprofloxacin is one of a new generation of fluorinated quinolones structurally related to nalidixic acid. The primary mechanism of action of ciprofloxacin is inhibition of bacterial DNA gyrase. It is a broad spectrum antibacterial drug to which most Gram-negative bacteria are highly susceptible in vitro and many Gram-positive bacteria are susceptible or moderately susceptible. Unlike most broad spectrum antibacterial drugs, ciprofloxacin is effective after oral or intravenous administration. Ciprofloxacin has been most extensively studied following oral administration. It attains concentrations in most tissues and body fluids which are at least equivalent to the minimum inhibitory concentration designated as the breakpoint for bacterial susceptibility in vitro. The results of clinical trials with orally and intravenously administered ciprofloxacin have confirmed the potential for its use in a wide range of infections, which was suggested by its in vitro antibacterial and pharmacokinetic profiles. It has proven an effective treatment for many types of systemic infections as well as for both acute and chronic infections of the urinary tract. Ciprofloxacin generally appeared to be at least as effective as alternative orally administered antibacterial drugs in the indications in which they were compared, and in some indications, to parenterally administered antibacterial therapy. However, further studies are needed to fully clarify the comparative efficacy of ciprofloxacin and standard antibacterial therapies. Bacterial resistance to ciprofloxacin develops infrequently, both in vitro and clinically, except in the setting of pseudomonal respiratory tract infections in cystic fibrosis patients. The drug is also well tolerated. Thus, as an orally active, broad spectrum and potent antibacterial drug, ciprofloxacin offers a valuable alternative to broad spectrum parenterally administered antibacterial drugs for use in a wide range of clinical infections, including difficult infections due to multiresistant pathogens.

Ciprofloxacin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.

Study design Review. Objective To formally introduce "degenerative cervical myelopathy" (DCM) as the overarching term to describe the various degenerative conditions of the cervical spine that cause myelopathy. Herein, the epidemiology, pathogenesis, and genetics of conditions falling under this hypernym are carefully described. Summary of background data Nontraumatic, degenerative forms of cervical myelopathy represent the commonest cause of spinal cord impairment in adults and include cervical spondylotic myelopathy, ossification of the posterior longitudinal ligament, ossification of the ligamentum flavum, and degenerative disc disease. Unfortunately, there is neither a specific term nor a specific diagnostic International Classification of Diseases, Tenth Revision code to describe this collection of clinical entities. This has resulted in the inconsistent use of diagnostic terms when referring to patients with myelopathy due to degenerative disease of the cervical spine. Methods Narrative review. Results The incidence and prevalence of myelopathy due to degeneration of the spine are estimated at a minimum of 41 and 605 per million in North America, respectively. Incidence of cervical spondylotic myelopathy-related hospitalizations has been estimated at 4.04/100,000 person-years, and surgical rates seem to be rising. Pathophysiologically, myelopathy results from static compression, spinal malalignment leading to altered cord tension and vascular supply, and dynamic injury mechanisms. Occupational hazards, including transportation of goods by weight bearing on top of the head, and other risk factors may accelerate DCM development. Potential genetic factors include those related to MMP-2 and collagen IX for degenerative disc disease, and collagen VI and XI for ossification of the posterior longitudinal ligament. In addition, congenital anomalies including spinal stenosis, Down syndrome, and Klippel-Feil syndrome may predispose to the development of DCM. Conclusion Although DCMs can present as separate diagnostic entities, they are highly interrelated, frequently manifest concomitantly, present similarly from a clinical standpoint, and seem to be in part a response to compensate and improve stability due to progressive age and wear of the cervical spine. The use of the term "degenerative cervical myelopathy" is advocated. Level of evidence 5.

Degenerative Cervical Myelopathy: Epidemiology, Genetics, and Pathogenesis.

Legionnaires’ disease is an important cause of community-acquired and hospital-acquired pneumonia. Although uncommon, Legionnaires’ disease continues to cause disease outbreaks of public health signifi cance. The disease is caused by any species of the Gram-negative aerobic bacteria belonging to the genus Legionella; Legionella pneumophila serogroup 1 is the causative agent of most cases in Europe. In this Review we outline the global epidemiology of Legionnaires’ disease, summarise its diagnosis and management, and identify research gaps and priorities. Early clinical diagnosis and prompt initiation of appropriate antibiotics for Legionella spp in all patients with communityacquired or hospital-acquired pneumonias is a crucial measure for management of the disease. Progress in typing and sequencing technologies might additionally contribute to understanding the distribution and natural history of Legionnaires’ disease, and inform outbreak investigations. Control of Legionnaires’ disease outbreaks relies on rapid ascertainment of descriptive epidemiological data, combined with microbiological information to identify the source and implement control measures. Further research is required to defi ne the actual burden of disease, factors that infl uence susceptibility, key sources of infection, and diff erences in virulence between strains of Legionella species. Other requirements are improved, specifi c, sensitive, and rapid diagnostic tests to accurately inform management of Legionnaires’ disease, and controlled clinical trials to ascertain the optimum antibiotics for treatment.

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Epidemiology and clinical management of Legionnaires' disease.

Human cytochromes P450

https://www.ajkd.org/article/S0272-6386(86)80112-3/pdf

Nephrotoxicity Induced by Cancer Chemotherapy With Special Emphasis on Cisplatin Toxicity

Clinical resistance to long-term oral ciprofloxacin

Soft tissue cervical spinal injuries occurred in 179 out of 1197 consecutive victims of road traffic accidents who needed to attend hospital; an incidence of 15 per cent. It was most common in female (P less than 0.01), restrained car occupants (P less than 0.05) in the 40-49 years age group (P less than 0.025). It was less common in rear seat passengers (P less than 0.001). Most were victims of collisions from the rear but significant numbers also occurred in other types of accidents. The incidence of associated injuries was low.

Soft tissue cervical spinal injuries in motor vehicle accidents.

Sternal fractures occurred in 78 out of 2097 consecutive victims of road traffic accidents who required to attend hospital; an incidence of 3.7 per cent. They were most common in restrained, front seat vehicle occupants involved in frontal collisions, and their frequency increased with age. There was a positive association with visceral chest injury but the latter was not thought to be the cause of death in any individual. Follow-up of survivors 2-4 years later revealed potential cardiac sequelae in 6 per cent.

Fracture of the sternum in motor vehicle accidents and its association with mediastinal injury.

Synovium in tissue culture has a degradative effect on cartilage which is partly chemically mediated. This effect has been shown to be more marked in the inflammatory arthropathies. The possibility of similar effects of haemophilic synovium were investigated.



Synovial tissue from patients with either chronic haemophilic arthropathy, rheumatoid arthritis or no inflammatory arthropathy was cultured. The prostaglandin production of the tissue in culture, and the effects of the haemophilic synovium conditioned medium (HCM) on human cartilage were compared.



Results show that haemophilic synovium produces prostaglandin E in culture, at markedly higher levels (upto 872 pg/mg synovium/hour n = 11) compared with normal (maximum 217 pg/mg/hour; n = 3). The HCM also stimulated glycosaminoglycans breakdown and decreased retention of newly synthesised chondroitin sulphate (CS) in cartilage cultured in it when compared to the normal conditioned medium (NCM). Expressed as a percentage of CS in the whole culture system after 14 days co-culture, CS lost from the cartilage compared to controls was 11.7% (S.E. 3. 4, n = 6) for HCM and 1.8% (S.E. 0.6 n = 4) for NCM. In comparison in two rheumatoid conditioned media (RCM) the loss was 14.7% and 12.6%. a similar effect has been demonstrated for haemophilic synovium as has previously been reported for rheumatoid synovium.

P.D.McLardy Smith

Papers

Clinical resistance to long-term oral ciprofloxacin

Soft tissue cervical spinal injuries in motor vehicle accidents.

Fracture of the sternum in motor vehicle accidents and its association with mediastinal injury.

A Tissue Culture Model of Cartilage Breakdown In Haemophilic Arthropathy