Inhalation of products of combustion

The atmosphere of a fire is deadly to breathe. Firefighters or building occupants may be victims of the heat, irritating smoke, depleted oxygen, carbon monoxide, and such other toxic gases as cyanide, hydrogen chloride, and acrolein. Increasing numbers of homes and public buildings are being built and furnished with highly flammable synthetic materials that give off copious smoke and toxic gases when burned. Whether or not there are cutaneous burns, the possibility of inhalation injury must be considered in any fire victim. All victims of a fire environment should be presumed to have CO intoxication and should be treated with 100% oxygen until the HbCO level is within normal limits. In an extreme situation, cyanide intoxication should be suspected and administration of sodium thiosulfate may be lifesaving. Upper airway occlusion may result from thermal damage or edema secondary to burns from soluble toxic gases. Chemical injury to the lower airway and alveoli may result from inhalation of insoluble irritant gases and toxic gases adsorbed on carbon particles. Upper respiratory tract obstruction may be suggested by the clinical presentation (eg, pharyngeal burns, stridor, hoarseness, dysphagia), but only by means of fiberoptic bronchoscopy can it be recognized or excluded with certainty. Intubation may be necessary. Lower respiratory tract injury may be manifest clinically by dyspneas, wheezing and chest tightness, as well as by hypoxemia and reduced FEV1 and FVC. Treatment is symptomatic, but close observation for progressive respiratory insufficiency is necessary.     

Metabolic changes with antihypertensive therapy of the salt-sensitive patient

Recent evidence suggests that metabolic changes that occur with antihypertensive agents may influence cardiovascular risk. Diuretic therapy is particularly appropriate for the salt-sensitive hypertensive patient. However, diuretic-induced electrolyte abnormalities may lead to ventricular arrhythmias, even in patients with uncomplicated essential hypertension. Antihypertensive drugs may change circulating lipoprotein levels, which may influence the development of atherosclerosis. Therefore, serum cholesterol and triglyceride levels should be monitored when antihypertensive drugs are administered that can cause hyperlipidemia. Weight reduction and diet therapy should be used because these may have a greater effect on reducing hyperlipidemia, though choice of antihypertensive agents is important. In addition, glucose tolerance may worsen with thiazide therapy, perhaps because newer evidence suggests that insulin resistance is common in essential hypertension. This glucose intolerance may be corrected with potassium repletion or substitution of bumetanide for thiazide. The calcium antagonists may be substituted for diuretic therapy, or other classes of antihypertensive drugs may be used with a reduced dose of diuretic drug if these metabolic changes persist. Thus, attention to metabolic changes may be as important as blood pressure reduction in treatment of the salt-sensitive hypertensive patient.     

Pulmonary fat embolism: a complication of fracture.

Medical personnel must be aware of the possibility of fat embolism as a complicating factor of fractures. Ambulance, emergency room, orthopedic, and intensive-care personnel may frequently be involved in the care of these patients. Fat embolism should be suspected any time a patient exhibits bizarre mental, pulmonary, or circulatory symptoms following a fracture. Prevention may be achieved by as near immobilization of a fracture as possible. When fat embolism does occur, the course of the illness may or may not be complex. The treatment is supportive and the patient should be made as comfortable as possible.     

Clinical manifestations of acromegaly.

Acromegaly is an uncommon disorder and may present in a variety of ways, leading to considerable delay in diagnosis. Unlike other pituitary tumors, tumors associated with acromegaly tend to be fairly large in most patients. Thus, symptoms may be commonly due to the tumor mass as well as to hormone oversecretion. Mortality is two- to threefold increased due to cardiovascular, respiratory, and neoplastic causes. An increase in diabetes mellitus and hypertension may contribute to the first of these. Early treatment may reverse the diabetes, soft tissue changes, sleep apnea, cardiovascular disease, and neuromuscular disease. The effect of early treatment on neoplasia is unclear, and patients probably should continue to be screened, especially for colon neoplasia, even after appropriate therapy for the acromegaly. Hypopituitarism may be present initially as a result of tumor mass but may also develop as a result of ablative therapy.     

Current overview of statin-induced myopathy

Statins are an efficacious and well-tolerated class of lipid-altering agents that have been shown to reduce the risk of initial and recurrent cardiovascular events. However, cerivastatin was withdrawn from the world market because of its potential for severe myotoxic effects. Since the benefits of statin treatment outweigh the small risk of adverse events, statins remain the first-line therapy for lipid lowering and preventing atherosclerotic cardiovascular diseases. The risk of myopathy may be minimized with the appropriate choice of agent and by identifying patients at risk of myotoxic effects. Elderly or female patients, or those with concomitant medications or impaired metabolic processes, may be at increased risk and should be monitored closely. The risk of myopathy may also be inferred from the pharmacologic and pharmacokinetic properties of the statin used. Since myotoxic events are more frequent at higher doses, statins that are effective in reducing cholesterol levels and helping patients to reach target levels at start doses may be useful. The lipophilicity of a statin and its potential for drug-drug interactions may also help to determine the likelihood of muscular effects. Drug-drug interactions may be avoided by selecting a statin that does not share the same metabolic pathway.     

Histological classification of pituitary disease

Morphological features of pituitary disease are classified according to increased and decreased hormone production to allow clinical correlation with pathological processes. Increased hormone synthesis and secretion may be due to pituitary adenomas or carcinomas derived from the five hormone-secreting cell types, or to extrapituitary stimuli causing hypertrophy and hyperplasia of those cells. Various tumour-like conditions can mimic functioning adenomas. Rarely, no lesion is detected and intrinsic abnormalities of adenohypophyseal cells are implicated. Hypopituitarism can be selective or generalized. Diffuse hormone deficiency is usually attributable to tissue destruction by tumours, inflammatory or infiltrative conditions or vascular lesions. Congenital abnormalities of pituitary development may result in hypophyseal dysfunction. Hypothalamic abnormalities may cause generalized hypopituitarism or may involve only selective releasing factors and hormones. Feedback inhibition and receptor abnormalities may be implicated in pituitary hypofunction, and selective deficiencies may be the result of genetic abnormalities, immune reactions or toxic damage to one cell type.     

Angiographic assessment of the culprit coronary artery lesion before acute myocardial infarction

Serial angiographic studies of patients with myocardial infarction and unstable angina suggest that the culprit plaque underlying a thrombus need not have produced severe luminal obstruction before onset of the event. An atherosclerotic coronary artery lesion can, therefore, have 2 important characteristics. First, it may be obstructive. Second, it may be "vulnerable" in that it has the potential to become thrombogenic if exposed to the appropriate triggering stimulus. A lesion need not be obstructive to become thrombogenic, nor do all obstructive lesions have thrombogenic potential. The cause of an infarction may thus be rupture of a nonobstructive plaque leading to occlusive thrombus formation. Because it may be difficult to predict the site of a subsequent occlusion from a coronary angiogram, coronary bypass surgery or angioplasty directed only at discernible stenotic lesions may not be effective for preventing subsequent myocardial infarctions. Appropriate therapy may need to be directed at the entire coronary tree. Such therapy might include cholesterol lowering, beta blockade and aspirin.     

On variability of effects for a metaanalysis of rheumatoid arthritis radiographic progression

Variance of an outcome that is the topic of a metaanalysis may be estimated in a variety of ways. Variances are also not used in the same way in every metaanalysis. The metaanalysis may be of a single measure expressed in its original units, or of several such measures simultaneously, or it may be done using unitless effect sizes. We present some observations and practical recommendations on the estimation and use of variances relating to these several approaches to metaanalysis, as they may apply in a metaanalysis of radiographic progression in rheumatoid arthritis.     

Cystic diseases of the liver and biliary tract (except for hydatid cyst). Role of surgery

The role of surgery in cystic diseases of the liver and biliary tract depends upon the kind of cysts. When they are symptomatic, solitary cysts of the liver may require laparoscopic unroofing. Mucinous cystadenoma should be resected since there is a risk of cystadenocarcinoma. Polycystic liver disease may require surgery when massive hepatomegaly results in pain or a worsening of the patient's general condition. Laparoscopic fenestration and partial hepatectomy are only indicated in a small number of selected patients with large or localized cysts. Orthotopic liver transplantation may be recommended in symptomatic cases with massive hepatomegaly even if there is no renal failure and no need for renal transplantation. Caroli's syndrome localized in one lobe or one segment should be resected since it leads to cholangiocarcinoma in more than 10% of cases. When cystic dilatations are diffuse, liver transplantation may be required. Choledochal cysts should be completely resected since cancer may arise in non resected parts. Complete resection may be associated with major hepatectomy.     

Nutritional therapy of irritable bowel syndrome

Nutritional factors relative to IBS include diagnostic and therapeutic considerations. Etiologically, foods do not cause IBS. A small percentage of patients with childhood allergic diatheses, usually in association with atopic dermatitis and asthma, may be intolerant to one or more of wheat, corn, dairy products, coffee, tea, or citrus fruits. Diagnostically, many patients labeled as IBS subjects are in fact intolerant to the ingestion of lactose-containing foods, sorbitol, fructose, or combinations of fructose and sorbitol. A precise dietary history will characterize this group. Taken in its broadest context, IBS involves the entire hollow tract inclusive of esophagus, stomach, small bowel, and colon. The symptomatic presentation relative to the hollow organ involved allows the selection of dietary manipulations that may help to reduce symptoms. Gastroesophageal reflux, a consequence of low LES pressure in some IBS patients, may be treated with the elimination of fatty foods, alcohol, chocolate, and peppermint. Delayed gastric emptying may be helped by the elimination of fatty foods and reduction of soluble fiber. Aberrant small bowel motor function may be ameliorated by reduction of lactose, sorbitol, and fructose and the addition of soluble fiber. Gas syndromes may be improved by reduced intake of beans, cabbage, lentils, legumes, apples, grapes, and raisins. Colonic motor dysfunction may be overcome by the gradual addition of combinations of soluble and insoluble fiber-containing foods and supplements. The selective use of activated charcoal and simethicone may be helpful.     

Preoperative diagnosis of pancreatic carcinoma by percutaneous aspiration biopsy

Carcinoma of the pancreas and chronic pancreatitis may be extremely difficult to differentiate by standard diagnostic methods preoperatively as well as at the operating table. Operative pancreatic biopsy may have a high morbidity, rare mortality, and can be misleading. Percutaneous aspiration biopsy may be of great potential benefit. It provides additional histological material not usually available, and an accurate diagnosis of malignancy can be made. In select patients a needless laparotomy may be avoided. It appears to be a safe procedure that should be considered in the evaluation of the patient with suspected pancreatic malignancy in which a mass lesion is demonstrated by ultrasonography, computerized tomography, angiography, or retrograde pancreatography.     

Misleading pains in the lower limbs of rheumatologic origin

Pain in the lower limbs related to rheumatic disease may be the source of diagnostic difficulties when it presents in the guise of pseudo-vascular manifestations. A narrow spinal canal and atypical neuralgia may present a very misleading clinical picture. Similarly, traumatic muscular pathology and bone trauma and tumours may also be misleading. A popliteal cyst and reflex sympathetic dystrophy may simulate venous disorders. Iatrogenic disease, particularly complications of anticoagulant treatment also need to be recognized.     

Immunodiagnosis of malaria

Different approaches to immunodiagnosis of malaria in an endemic country have been described in this paper. Demonstration of circulating malaria antigen may be done by gel-diffusion and counter-immunoelectrophoresis. Parasite associated antigen may be demonstrated by highly sensitive methods like radio-immunoassay or enzyme linked immuno sorbent assay. Malaria antibodies of the IgG type being long lasting do not appear to have any role in immuno-diagnosis. However, determination of malaria specific IgM antibodies by P. gallinaceum haemagglutination test or IgM immunofluorescence test may be simple and useful in immunodiagnosis of malaria. The tests though evaluated in different laboratories may not be applicable in the field for diagnosis of malaria at the present moment. However, it is envisaged that with the availability of different specificities of monoclonal antibodies by way of hybridoma technology and also with the help of recombinant DNA techniques immunodiagnosis of malaria in the field situation may become a reality.     

Management of genital herpes simplex infection

Herpes simplex infection of the genitals is a common condition, more often due to herpes simplex virus (HSV) type 2 than to type 1 virus. There is a severe first attack followed by mild recurrences which are more common and more frequent after HSV-2 than after HSV-1 genital infection. Clinical features with prodrome, vesicles and erosions may be characteristic allowing rapid clinical diagnosis. When possible laboratory confirmation should be attempted. General management includes simple hygiene, avoidance of sexual transmission, use of condoms, and notifying partners. Oral acyclovir (Zovirax, Wellcome) is the drug of choice for initial attacks and should be considered for all women with this diagnosis. Intravenous acyclovir may be used for very severe attacks. Men with initial attacks may be treated with oral acyclovir but mild disease affecting only skin may be treated with 5% acyclovir cream. Recurrences are short so acyclovir has less effect. Frequent recurrences can be troublesome and may be suppressed by continuous oral acyclovir, or individual attacks may be aborted with intermittent therapy. Various systemic complications may occur; an important but rare problem is primary herpes in late pregnancy. Acyclovir is effective in the treatment of the troublesome herpes simplex disease associated with human immunodeficiency infection. Acyclovir is one of the more expensive treatments for sexually transmitted diseases. At present in many countries costs are being examined, and application of the principles outlined here should help to minimize cost and maximize care.     

Experimental models of heart failure

Experimental models of heart failure can be used to address specific questions not easily answered in patients, but no single model can reproduce exactly any of the clinical syndromes of heart failure since these are dominated by fatigue and breathlessness. Heart failure may be induced experimentally by pressure loading, volume loading, myocardial infarction, or by the creation of other disease states within the myocardium. Pressure loading may be especially useful in the study of ventricular hypertrophy, cellular derangements and vascular changes. Volume loading may be useful when examining the pathogenesis of hormone and electrolyte disturbances. Models of myocardial infarction or destruction are likely to be the most suitable for assessing novel therapy provided that peripheral reflexes are maintained. Experimental cardiomyopathy can provide an important means of identifying pathological subcellular mechanisms. They may be of use in the evaluation of vasodilator drugs but caution should be exercised in the study of inotropic agents. Any one model may be useful if it permits study of a single factor or variable in isolation or at a time when information is not obtainable from patients. For greatest clinical relevance, studies should be made in conscious animals with intact reflexes.     

Basic considerations in the reversal of atherosclerosis: significance of high-density lipoprotein in stimulating reverse cholesterol transport

Atherosclerotic cardiovascular disease in the elderly is the result of several decades of cholesterol accretion. Advanced lesions may not be amenable to treatment, but a reversal of cholesterol accumulation may be possible. High-density lipoproteins (HDL) could serve an important function in this reversal through their role in the process of reverse cholesterol transport, which removes cholesterol from the body. Reverse cholesterol transport could be stimulated by raising plasma HDL level, but the efficacy of the process may be determined by the way in which HDL level is elevated. The increase of HDL synthesis rate may be the best approach. The antiatherosclerotic effects of gemfibrozil, a lipid-lowering agent that appears to raise HDL synthesis rate, may be mediated through this mechanism.     

Pathways of cell activation in spondyloarthropathies

The initiating event in cell activation is unknown in most autoimmune diseases. The role of infection is clear in some cases, especially in reactive arthritis; however, there is little evidence of a specific organism in other spondyloarthropathies. Common pathways of cell-cell interaction and activation manifest in inflammation, but subtle differences may exist. The presence of T cells, macrophages, and B-lymphocytes suggest an autoimmune mechanism; the arthritogenic peptide theory has been proposed. Furthermore, the association of spondyloarthropathies with HLA-B27 suggests it may be important in synovial T-cell activation. Other cell types involved in the process of bone and cartilage destruction, including fibroblasts and osteoclasts, may also be activated. Endothelial activation and angiogenesis may be a critical primary event in these diseases. Finally, trauma (physical or psychological) in the form of stress may be an important factor; the nervous system and neuropeptides may play a role in cell activation and initiation of arthritis.     

Is insulin a factor in the genesis of the vascular complications of diabetes?

Several recent studies report that insulin may be a pathogenic factor in cardiovascular disease and the vascular complications of diabetes. The route of administration of insulin may be partially responsible for vascular side effects that occur in the management of diabetes. These side effects may be overcome by the development of a more physiologic route of administration than by subcutaneous injection.     

Interferon and cytotoxic chemotherapy for the treatment of post-transplant lymphoproliferative disorder

Abstract: Interferon-α and cytotoxic chemotherapy may be effective treatment modalities for the post-transplant lymphoproliferative disorder. Interferon-α may result in a complete response in up to 40% of patients, while chemotherapy may be effective in 75% of those failing local surgical excision, a reduction in immunosuppression, and an antiviral agent. Interferon may be used early after diagnosis in patients with relatively slowly growing tumors. Chemotherapy should be selected for patients with bulky, rapidly growing malignancies. The toxicity of chemotherapy may be minimized by discontinuing maintenance immunosuppression during chemotherapy, administering GCSF, and providing antimicrobial prophylaxis. Rejection is minimized by the reintroduction of maintenance immunosuppression when the patient is no longer neutropenic.     

Consideration of conduit and resistance vessels in regulation of blood flow

In heart failure the maximal capacity for dilation, especially in skeletal muscle arteries, is reduced. This may be due to changes in sympathetic tone, in hormonal stimulation (both by circulating and intramurally released compounds like angiotensin II with additional presynaptic effects) or in endothelium mediated vasodilation. The loss of endothelium-mediated, flow-dependent dilation in large arteries may originate from endothelial impairment induced by, e.g., chronic hypoxia or hypercholesterolemia. Similar effects result from suppressed local dilator autacoid release brought about, e.g., by circulating atrial natriuretic factor in the presence of a fully functioning endothelium. Finally, attenuated augmentations in flow may be secondary to changes in muscular metabolism, and an increased alpha-adrenergic neurogenic constriction may be present. This may be further enhanced by a local, beta-receptor-mediated angiotensin II release. An impaired dilation at the level of resistance vessels may result from a combination of the mechanisms listed above.