Nelfinavir desensitization.

OBJECTIVE: To report the first case of nelfinavir desensitization in an HIV patient who was intolerant to protease inhibitors. CASE SUMMARY: A 43-year-old HIV-positive white man was treated with several protease inhibitors. The patient developed rashes in response to all protease inhibitors. His viral load was controlled only in the presence of a protease inhibitor. The patient tolerated nelfinavir longer than the other agents; therefore, the decision was made to attempt to desensitize him to nelfinavir. A six-hour inpatient protocol was used, and he tolerated the procedure without event. His disease is now well managed without recurrence of the rash. DISCUSSION: The use of protease inhibitors has had a major impact on the morbidity and mortality of HIV-infected patients, Despite their benefits, this class of drugs is not without adverse effects. Allergic reactions in the form of rashes may develop, which can severely limit treatment options in HIV patients. We report the first case of rapid desensitization of nelfinavir in a patient who developed rashes to several protease inhibitors. CONCLUSIONS: Intolerance to protease inhibitors due to rash is a well-documented phenomenon. In HIV patients, this can limit treatment options severely. This case demonstrates how desensitization to nefinavir can be performed successfully.

Original memoirs: the control of bleeding in operations for brain tumors: with the description of silver "clips" for the occlusion of vessels inaccessible to the ligature. 1911.

One of the chief objects of concern in intracranial surgery should be the avoidance of any unnecessary loss of blood, for at best, in many cases of brain tumor associated with venous stasis, bleeding is likely to be so excessive as to necessitate postponement of the final steps of the procedure until a second or even a third session. The common methods of blood stilling by sponge, clamp, and ligature are largely inapplicable to intracranial surgery, particularly in the presence of bleeding from the nervous tissues themselves, and any device which serves as an aid to hemostasis in these difficult operations will bring a number of them to a safe termination at a single sitting, with less loss of blood and less damage to the brain itself. In addition to the more familiar tourniquet for the scalp, and wax for diploetic and emissary bleeding, suggestions are offered as to the use of gauze pledgets, dry sterile cotton, fragments of raw muscle and other tissues, as well as sections of organizing blood-clots for superficial meningeal bleeding, and silver "clips" for inaccessible individual points ether in dura or brain. The successful consummation of any critical operation often depends upon seeming trifles. It is, however, the scrupulous observance of surgical minutiae that makes possible the safe conduct of major intracranial performances--performances which a few years ago were attended in most cases by a veritable dance Macaber.

Lactic acidosis secondary to nucleoside analogue antiretroviral therapy.

A 53-year-old woman with newly diagnosed HIV infection was treated with the nucleoside analogue antiretroviral agents lamivudine and stavudine and the protease inhibitor indinavir. An illness characterized by severe lethargy, persistent nausea and vomiting, lactic acidosis, hyperglycemia, and microvesicular hepatic steatosis developed. Her symptoms improved gradually after withdrawal of the antiretroviral agents. The illness can be explained by mitochondrial dysfunction caused by inhibition of mitochondrial DNA (mtDNA) polymerase by the nucleoside analogues. The patient was successfully treated with nonnucleoside reverse transcriptase inhibitors, which lack affinity for mtDNA polymerase.

Reprint of "Concerning Surgical Intervention for the Intracranial Hemorrhages of the New-born" by Harvey Cushing, M.D. 1905.

This paper was first presented at a meeting in 1905 and gives an insight into the problems faced in early neurosurgical operations in newborns and the way they were approached by an adventurous surgeon.

Acute tubulointerstitial nephritis attributable to indinavir therapy.

Indinavir sulfate has been reported to cause asymptomatic crystalluria and nephrolithiasis in patients with human immunodeficiency virus (HIV) infection. Patients taking indinavir may present with asymptomatic crystalluria, nephrolithiasis with frank renal colic and obstruction, flank pain in the absence of nephrolithiasis, and dysuria or urgency. Asymptomatic crystalluria has been described as benign. Discontinuation of the drug has not been recommended in the absence of nephrolithiasis. We report two HIV-positive patients receiving indinavir who developed acute interstitial nephritis with foreign body giant cell reaction on renal biopsies. Both patients had asymptomatic crystalluria, although crystals were associated with clumps of white blood cells (WBCs) on urinalysis in one patient. Both cases show that the inflammatory response was significant enough to lead to tubular injury and acute renal impairment. Our findings suggest that asymptomatic crystalluria attributable to indinavir may illicit an inflammatory response with acute renal insufficiency, warranting monitoring of renal function, especially in patients with crystalluria.

Pyomyositis in the acquired immunodeficiency syndrome.

Pyomyositis, a purulent infection of skeletal muscle, is usually caused by Staphylococcus aureus. Many cases of pyomyositis in human immunodeficiency virus (HIV) seronegative patients have been reported in North America and have been reviewed extensively. Moreover, pyomyositis has been reported in association with HIV infection in patients with or without the acquired immunodeficiency syndrome (AIDS). We describe two patients with pyomyositis and HIV and review the available English language literature. Leukocytosis and bacteremia tend to occur less frequently in those with HIV infection and pyomyositis. However, fever, S aureus infection, and bilateral involvement occur more frequently in HIV-positive patients. Antibiotic therapy together with surgical drainage or aspiration is usually sufficient.

Hypercalcemia as an early sign of lymphoma in a patient with acquired immunodeficiency syndrome (AIDS).

Hypercalcemia is uncommon in patients infected with the human immunodeficiency virus (HIV). It has been described in association with cytomegalovirus infection, Pneumocystis carinii pneumonia, granulomatous diseases, and lymphoma. However, symptomatic hypercalcemia as an early sign of an underlying AIDS-related lymphoma is not well documented. We discuss the case of a patient with HIV and hypercalcemia, leading to the diagnosis of an underlying lymphoma. The hypercalcemia was associated with a suppressed serum level of intact parathyroid hormone and a normal serum phosphorus level. The possibility of a lymphoproliferative disorder should be considered in the differential diagnosis of HIV-associated hypercalcemia.

Therapeutic failure of trimethoprim/sulfamethoxazole in the treatment of Pneumocystis carinii pneumonia.

OBJECTIVE: To report a case of failure of treatment of Pneumocystis carinii pneumonia (PCP) with trimethoprim/sulfamethoxazole (TMP/SMX) in a patient with HIV infection, despite an adequate serum SMX concentration. CASE SUMMARY: A 52-year-old white man was treated with TMP/SMX for PCP. After discharge he returned to the hospital with worsening of the PCP despite a serum SMX concentration of 60 micrograms/mL 18 hours after his last dose of TMP/SMX. DISCUSSION: PCP is one of the most common complications of HIV infection. TMP/SMX is the drug of choice for prophylaxis and treatment. The causes of therapeutic failure with this agent are not well documented. CONCLUSIONS: Alternative therapies to TMP/SMX should be seriously considered if the serum concentrations are therapeutic and the patient is not clinically improved.

Successful vancomycin desensitization in a patient with end-stage renal disease and anaphylactic shock to vancomycin.

OBJECTIVE: To report successful desensitization in a patient with a history of end-stage renal disease (ESRD) and anaphylactic shock after receiving vancomycin. CASE SUMMARY: A 47-year-old white woman with a history of ESRD was admitted to the hospital reporting persistent nausea, vomiting, and diffuse abdominal pain. She had developed anaphylactic shock after exposure to vancomycin 3 years prior to this hospitalization. The patient's hospital course was complicated by septic shock and positive blood cultures for methicillin-resistant Staphylococcus epidermidis. The patient tolerated vancomycin desensitization and received intravenous vancomycin 100 mg/d for 21 days. DISCUSSION: The desensitization protocol used in this report allows for gradual increases in vancomycin serum concentrations, avoiding peak and trough concentrations that occur with intravenous boluses. Maintaining the desensitized state is dependent on the continuous presence of the antigen with a return of clinical sensitivity after drug discontinuation. The vancomycin desensitization protocol and subsequent dosing strategy was used to ensure the continuous presence of vancomycin at steady-state concentrations to prevent the return of anaphylactic sensitivity. CONCLUSIONS: Desensitization was successful in a patient with ESRD and history of anaphylactic shock to vancomycin.

Severe adenoviral nephritis following bone marrow transplantation: successful treatment with intravenous ribavirin.

Invasive adenovirus infection is recognized as an unusual cause of serious end-organ sequelae following BMT. Because symptomatic therapy may be inadequate for more serious infections, the use of investigational agents is justified. We describe a case of severe, progressive nephritis secondary to adenovirus serotype 11 following BMT. Treatment with i.v. ribavirin led to prompt clinical improvement and resolution of adenovirus excretion.

Medical Classic. The functions of the pituitary body: Harvey Cushing.

It may be said that the pituitary body is a double organ in the sense that the secretion of its anterior and solidly epithelial portion discharges into the blood sinuses which traverse this part of the gland; whereas the hyaline substance, apparently the product of secretion from the epithelial investment of the posterior lobe, enters the cerebrospinal space by way of channels in the pars nervosa. Though possessing a physiologically active principle, as shown by the results of injections, the secretion of the posterior lobe does not seem to be so vitally essential to physiological equilibrium as that of the anterior lobe, the total removal of which leads to death with a peculiar train of symptoms which set in at an early date in the adult and after a longer interval in younger animals. Alterations in the gland, which often ultimately assume the character of a malignant growth (adenoma) but which presumably, at least in their earlier stages, represent an hypertrophy, are common in clinical conditions of overgrowth (akromegaly and gigantism), and certain feeding experiments lend support to the view that these clinical states represent the consequences of hyperactivity of the pars anterior. Partial removals of the anterior lobe usually lead to obvious disturbances of metabolism accompanied oftentimes by adiposity and in the young by a persistence of infantilism, or in adults by a tendency top lose the secondary sexual characteristics already acquired. These experimental conditions are comparable to those which have been recognized clinically as accompaniments likewise of tumors in the hypophyseal region, which under these circumstances can therefore be interpreted as lesions which through pressure have led to lessened glandular activity. In view of the apparent interrelation of many of the glands of internal secretion it is quite probable that certain of the symptoms known to accompany hypophyseal disease may be consequent upon a secondary change in other glands which follows the primary lesion of the hypophysis. These changes are seemingly more outspoken and more widespread after a lesion of the pituitary body than after a corresponding lesion of any other individual member of the group of ductless glands, and in view of its unusually well-protected position one might have conjectured that it must represent a vitally important organ.