Hyperglycemic Episodes Are Associated With Postoperative Infections After Cardiac Surgery.

BACKGROUND AND AIMS: To describe the incidence of and risk factors for postoperative infections and the correlation between postoperative hyperglycemia despite tight blood glucose control with infectious and other complications after contemporary cardiac surgery. MATERIAL AND METHODS: The study comprised 1356 consecutive adult patients who underwent cardiac surgery between January 2013 and December 2014 and were followed up for 6 months. Patients surviving the first 2 days were included in the analysis. Preoperative demographic information, medical history, procedural details, and the postoperative course were recorded. The target range for blood glucose levels was 4-7 mmol/L and repeated arterial blood samples were obtained during the intensive care unit stay. The associations of blood glucose levels during the first postoperative day and the occurrence of postoperative infections and other significant complications were analyzed. RESULTS: Of the study cohort, 9.8% developed infectious complications which were classified as major surgical site infections in 2.2%, minor surgical site infections in 1.1%, lung infections in 2.0%, unclear fever or bacteremia in 0.3%, cannula or catheter related in 2.6%, multiple in 1.5%, and other in 0.2%. The incidence of deep sternal wound infection was 2.0%. Repeated hyperglycemia occurred in 39.7% of patients and was associated with increased rates of postoperative infections, 12.1% versus 8.2%, p = 0.019; stroke, 4.9% versus 1.5%, p < 0.001; and mortality, 6.1% versus 2.1%, p < 0.001, when compared to patients with single or no hyperglycemia. CONCLUSION: Every 10th patient develops infectious complications after cardiac surgery. Repeated hyperglycemia is associated with increased rates of infectious complications, stroke, and mortality.

Primary hyperparathyroidism: a case report.

Primary hyperparathyroidism results from the excessive secretion of PTH and typically produces frank hypercalcaemia. With the advent of multiphasic screening of serum chemistries, it has been recognized that primary hyperparathyroidism is not an uncommon disorder. Here, a 32 years old lady with burning to colicky recurrent upper abdominal pain, polyuria, polydipsia associated with anorexia, dyspepsia, generalized body ache, joint pain, constipation and weight loss has been described. An initial abdominal ultrasound was performed at hospital and revealed features of cholelithiasis and bilateral nephrocalcinosis. Serum biochemistries revealed that her serum calcium was 12.60mg/dl, serum PTH was 222.80ng/dl, serum creatinine was 0.90mg/dl, 99 Tc-sestamibi scanning for parathyroid evaluation revealed features suggestive of parathyroid adenoma adjoining the lower pole of right lobe of thyroid gland. Bone densitometry of femur and spine by DEXA showed osteoporosis with T score value <-3.5 SD. Right hemithyroidectomy with parathyroid adenoma excision was performed. Patient was closely monitored. Serum calcium and parathyroid hormone levels were markedly reduced near to the normal range within two weeks of surgery. Following five months after surgery, serum PTH was 29.59ng/dl, six months after surgery serum calcium was 9.2mg/dl. Patient is now in good physical condition and under regular follow up.

Pathophysiology of cyclooxygenases in cardiovascular homeostasis.

Cyclooxygenase (COX) catalyzes the conversion of arachidonic acid into prostaglandin H(2) (PGH(2)), which is subsequently converted to the prostanoids PGE(2), PGI(2), PGF(2alpha), and thromboxane A(2). COX has 2 distinct membrane-anchored isoenzymes: COX-1 and COX-2. COX-1 is constitutively expressed in most normal tissues; COX-2 is highly induced by proinflammatory mediators in the setting of inflammation, injury, and pain. Inhibitors of COX activity include conventional nonselective nonsteroidal anti-inflammatory drugs and selective nonsteroidal anti-inflammatory drugs, such as COX-2 inhibitors. The adverse effects of COX inhibitors on the cardiovascular system have been addressed in the last few years. In general, COX inhibitors have many effects, but those most important to the cardiovascular system can be direct (through the effects of prostanoids) and indirect (through alterations in fluid dynamics). Despite reports of detrimental human cardiovascular events associated with COX inhibitors, short, long, and lifetime preclinical toxicology studies in rodents and nonrodents have failed to identify these risks. This article focuses on the expression and function of COX enzymes in normal and pathologic conditions of the cardiovascular system and discusses the cardiovascular pathophysiologic complications associated with COX inhibition.

Obstructive protein cast nephropathy in cynomolgus monkeys treated with small organic molecules.

We have observed a renal toxicity consistent with an obstructive protein cast nephropathy in cynomolgus macaques but not in other species treated with different therapeutic candidates having a common carboxylic acid moiety, suggesting a species-specific sensitivity. Here, we present renal toxicity findings consistent with a protein cast nephropathy in a 2-week safety study in cynomolgus monkeys. Light microscopic changes consisted of intratubular cast formation, tubular dilatation, interstitial inflammation, and expansion of the medullary interstitium. Tubular cast material was identified as Tamm-Horsfall protein (THP) and, on ultrastructure, crystalloid material was present in vacuoles of tubular epithelium. It is hypothesized that microcrystal formation in the urinary tubular spaces induces aggregation of THP protein and cast formation in monkeys. Drug-induced obstructive nephropathy is not identified as a major problem in humans; thus, the clinical relevance of the above findings in monkeys is not clear.

Skin wound healing in the SKH-1 female mouse following inducible nitric oxide synthase inhibition.

BACKGROUND: The inducible isoform of the nitric oxide (NO) synthase (NOS) enzyme (iNOS) is upregulated by inflammatory mediators and/or other pathological stresses, generating high, sustained levels of NO. Cumulative data suggest a role for NO in the regulation of skin wound healing, although it is not clear to what extent NO generated by iNOS, and possibly endothelial NOS (eNOS), contribute to that healing process. Because of the current lack of understanding regarding the contribution of iNOS in wound healing, as well as the lack of wound healing data available for SC-842, an iNOS inhibitor, this in vivo study was conducted to investigate the possible role of SC-842 in interfering with wound healing. OBJECTIVES: This study evaluated whether inhibition of iNOS affects incisional skin wound healing. METHODS: Using a cutaneous full-thickness, sutured, incisional wound model in hairless SKH-1 mice, the role of iNOS in the wound healing process was evaluated by comparing in vivo effects of the iNOS inhibitor, SC-842, at various doses that result in selective inhibition of iNOS as well as nonselective NOS inhibition (as evidenced by elevated blood pressure resulting in inhibition of eNOS and/or neuronal NOS). Dexamethasone was used as a positive control. RESULTS: There were no differences in wound healing at day 28 postwounding, as evaluated by tensile strength and histology, between SC-842- and vehicle-treated animals. A decrease in tensile strength was noted at day 14 postwounding in wounds from the mid- and high-dose-treated animals as compared with vehicle-treated animals, but this difference was slight and was not associated with histological differences from vehicle-treated controls. CONCLUSIONS: These data indicate that iNOS inhibition does not adversely affect the healing of incisional wounds in SKH-1 mice as assessed over 28 days by wound tensile strength and histology.

Effects of cyclooxygenase inhibition on bone, tendon, and ligament healing.

Cyclooxygenases (COX-1 and COX-2) catalyze the conversion of arachidonic acid to prostaglandins (PGs). PGs play a significant role in bone metabolism in health and disease. Conventional non-selective, non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors (COXIBs) are widely used in patients with musculoskeletal conditions and as a post-surgical analgesics. Due to their effects on PG synthesis, these drugs have been hypothesized to affect the healing process of bone fractures and orthopedic surgical sites. A variety of experimental models of bone, ligament, and tendon repair have assessed the effects of these selective and non-selective COX inhibitors in animals, but with variable outcomes. At this time, large-scale, robust clinical study data do not exist, limiting the relevant assessment of experimental animal data to humans. Here, we provide a critical review of available data on the role of PGs and the effect of COX inhibitors on bone, tendon, and ligament repair. Collectively, this assessment suggests potential involvement of PGs in the healing process of these tissues via modulation by non-selective NSAIDs and selective COX-2 inhibitors.

Epidemiology and management of heart failure and left ventricular systolic dysfunction in the aftermath of a myocardial infarction.

Robust epidemiological data on the incidence of myocardial infarction (MI) are hard to find, but synthesis of data from a number of sources indicates that the average hospital in the UK should admit about two patients with a first MI and one recurrent MI per 1000 population per year. Possibly the most relevant data on the incidence, prevalence, and persistence of post-MI heart failure can be derived from the TRACE study. Most patients will develop heart failure or major left ventricular systolic dysfunction (LVSD) at some time after an MI, most commonly during the index admission. In up to 20% of cases this will be transient, but such patients still have a poor prognosis. There is likely to be around one patient discharged per thousand population per year with heart failure or major LVSD after an acute MI. It is important to organise care structures to ensure that patients with post-MI heart failure and LVSD are identified and managed appropriately.

Characterization of cyclooxygenase-2 (COX-2) during tumorigenesis in human epithelial cancers: evidence for potential clinical utility of COX-2 inhibitors in epithelial cancers.

Increased prostaglandins (PGs) are associated with many inflammatory pathophysiological conditions; and are synthesized from arachidonic acid by either of 2 enzymes, cyclooxygenase-1 (COX-1) or -2 (COX-2). Recent epidemiologic, expression, and pharmacologic studies suggest COX-2 derived metabolites also play a functional role in the maintenance of tumor viability, growth and metastasis. Archival and/or prospectively collected human tissues were prepared for immunohistochemistry, and representative cases assayed via Western blot, RT-PCR, or TAQman analysis. Consistent overexpression of COX-2 was observed in a broad range of premalignant, malignant, and metastatic human epithelial cancers. COX-2 was detected in ca. 85% of the hyperproliferating, dysplastic, and neoplastic epithelial cells, and in the existing and angiogenic vasculature within and adjacent to hyperplastic/neoplastic lesions. These data collectively imply COX-2 may play an important role during premalignant hyperproliferation, as well as the later stages of invasive carcinoma and metastasis in various human epithelial cancers.

Morbidity associated with asthma and audit of asthma treatment in out-patient clinics.

A study was undertaken to determine the extent of morbidity associated with asthma and to audit the management of asthma in two out-patient clinics of two district hospitals. Patients were recruited for the study during a 3-month period from December 1990 to February 1991. Seventy asthmatic patients were studied. Eighty-six percent of the patients had their sleep disturbed by asthma, 77% took daily medication regularly, 63% felt that their activities were restricted by asthma, 60% had at least one acute exacerbation in the preceding six months. Of those who had their peak expiratory flow rate (PEFR) measured, 40% had a PEFR below 50% predicted, and only 11% had normal PEFR (greater than 80% predicted). The morbidity of asthma was thus considerable. On the other hand, the drug treatment of these asthmatics was grossly inadequate. They were prescribed on average 2.1 item of drugs, which for most patients comprised an oral beta agonist and a theophylline. Only 43% of the patients received inhaler therapy, but no patients were given steroids, inhaled or oral. The drug treatment was unrelated to the severity of patients' asthma. Further, objective measurement of severity was under-used in the assessment of asthma, only 8.5% of patients ever had their PEFR recorded. This study has found that asthma is poorly managed in out-patient clinics. We need to improve the training of doctors in the optimal management of asthma.

Therapeutic value of corticosteroid hormone in the treatment of diphtheria.

Two hundred and ten cases of diphtheria of both sexes and all ages with seasonal incidence and area prevalences were studied. Therapeutic trial of corticosteroid hormone was done in all cases of diphtheria studied. It was found that cortisone along with conventional drug therapy, the death rate came down to 68%. Age incidence of our cases had similar pattern with current literatures where as we observed some deviation in sex and seasonal incidence.