Oral trimethoprim-sulfamethoxazole in the treatment of cerebral toxoplasmosis in AIDS patients--a prospective study.

Toxoplasma encephalitis is the commonest cause of intracranial mass lesions in AIDS patients. Effective therapy includes pyrimethamine plus sulfadiazine, clindamycin with pyrimethamine, and co-trimoxazole. This study examines the efficacy of oral co-trimoxazole in 20 AIDS patients with toxoplasmosis and seeks to confirm the experience of Torre et al.     

Intracerebral toxoplasmosis in patients with acquired immune deficiency syndrome

The acquired immune deficiency syndrome (AIDS) is a recently described T-cell deficiency predisposing patients to a spectrum of opportunistic infections. Kaposi's sarcoma, and other neoplasms. It appears primarily among homosexual males and intravenous drug abusers, but is now being observed in other groups as well. The authors describe six adult patients with AIDS who developed intracranial toxoplasmosis. In four patients, diagnosis was made by brain biopsy, and in one by serology. These patients received a 90-day course of therapy with sulfadiazine, pyrimethamine, or both when tolerated, and improved neurologically. In one patient, the brain biopsy was nondiagnostic and the organism was identified at autopsy. On computerized tomographic and pathological follow-up studies the organism appeared to be eradicated by therapy. Early aggressive diagnostic study and prompt institution of therapy are imperative for reversal of neurological deficits. Despite cure of toxoplasmosis, the prognosis in patients with AIDS is poor; the mortality in this series was 67%. Isolation precautions should be taken by those caring for such patients.     

Toxoplasmosis after renal transplantation.

Infection is the main cause of death following renal transplantation. In the literature 7 fatal cases of toxoplasmosis following renal transplantation have been described. In the present papers a case of reactivated toxoplasmosis is presented where the patient survived. Fortuitous withdrawal of therapy and transplant nephrectomy may have been responsible for the patient's survival. The problems of diagnosis of toxoplasmosis following renal transplantation are discussed. Early diagnosis is vitally important as successful treatment of toxoplasmosis with pyrimethamine and sulfonamides in patients receiving immunosuppressive therapy has been reported. It is emphasised that reaction of toxoplasmosis should always be considered in patients with fever of unknown origin and cerebral symptoms.     

Use of CT and MR imaging to distinguish intracranial lesions and to define the need for biopsy in AIDS patients

To explore the potential usefulness of imaging studies in the diagnosis of focal central nervous system (CNS) lesions associated with acquired immunodeficiency syndrome (AIDS), the authors retrospectively examined the radiographic studies of 149 AIDS patients who presented with signs and symptoms of the three most common focal CNS lesions. Of these patients, 74 (50%) had Toxoplasma abscesses, 45 (30%) had primary CNS lymphoma, and 30 patients (20%) had progressive multifocal leukoencephalopathy (PML). Magnetic resonance (MR) imaging was more sensitive than computerized tomography (CT) in detecting lesions, especially in cases of PML. Whereas CT was unable to distinguish mass lesions caused by toxoplasmosis from those caused by lymphoma, 71% of the solitary lesions seen on MR images were lymphomas. These results indicate that empirical treatment for toxoplasmosis, the most common initial treatment for AIDS patients with neurological symptoms stemming from mass lesions, is not likely to be successful for patients with solitary lesions on MR images. Rather, early biopsy is advisable. If the presence of lymphoma is confirmed, the rapid initiation of treatment can allow prolonged high-quality survival.     

Intravesical pharmacotherapy for non-muscle-invasive bladder cancer: a critical analysis of currently available drugs, treatment schedules, and long-term results

OBJECTIVES: Review adjuvant intravesical pharmacotherapy for non-muscle-invasive bladder cancer (NMIBC), emphasising treatment schedules and long-term results. METHODS: Search of published literature on conventional treatment of NMIBC, emerging drugs, and device-assisted therapies. RESULTS: In low-risk NMIBC patients an immediate instillation with chemotherapy is sufficient. For patients with intermediate- or high-risk tumours, additional adjuvant instillations are needed. For intermediate-risk patients chemotherapeutic instillations, usually with mitomycin C or epirubicin, are safe and effective in reducing the risk of recurrence in the short term, but efficacy is only marginal in the long term. Newer drugs have promising results, but long term follow-up is limited or lacking. In these patients bacillus Calmette-Guérin (BCG) does not seem to be more effective, only more toxic. In high-risk NMIBC, or patients in whom chemotherapy fails, BCG is the best choice with lower rates of recurrence and progression. For BCG failures cystectomy is therapy of choice, although the combination of BCG and interferon-alpha can be considered, just as device-assisted therapies such as thermochemotherapy and electromotive drug administration. CONCLUSIONS: Risk-adapted first-line adjuvant therapy for NMIBC after TURBT is well established but has its limitations because recurrences are still numerous. Some new drugs and second-line therapies are promising, but efficacy should be confirmed.     

局部进展期胰腺癌新辅助治疗的现状与进展

胰腺癌恶性程度高,其总体5年生存率仅约11%。虽然根治性手术切除可能治愈胰腺癌,但仅约15%胰腺癌在首次确诊时为可切除性疾病。新辅助治疗使得有些原本不可切除的局部进展期胰腺癌（LAPC）获得了R0切除的机会。LAPC新辅助治疗是基于目前治疗现状的一种新的治疗模式,逐渐为临床外科医生接受。新辅助治疗方案的出现,使得20%～61%的LAPC经新辅助治疗后转化为可切除病例。奥沙利铂、伊立替康、氟尿嘧啶和亚叶酸钙（FOLFIRINOX）及吉西他滨联合白蛋白紫杉醇（AG）明显提高了LAPC的手术切除率,是LAPC首选一线新辅助治疗方案。各医疗中心关于LAPC新辅助治疗的方案选择、周期、评估指标、手术时机等方面仍存在较大差异。部分术前全身化疗不足以使肿瘤降期达到手术指征的LAPC患者,可将联合化放疗作为初始治疗。对于不能耐受系统性化疗的LAPC患者,可采用立体定向放射治疗（SBRT）控制局部肿瘤进展。胰腺癌的治疗靶点包括KRAS、EGFR、PARP及NTRK等。NCCN指南建议对所有LAPC患者进行基因检测,指导最佳药物治疗方案及参与新药的临床研究。胰腺癌免疫治疗主要包括免疫检查点抑制剂、过继性T...     

Combination pharmacotherapy in hypertension

Combination pharmacotherapy with two or more drugs is required in order to reach the currently recommended blood pressure goals in the majority of hypertensive patients, particularly those with a goal of <130/80 mm Hg. Further to the potentiation of the antihypertensive effects, benefits of combination therapy include the potential of fewer adverse affects and of improvement of patients’ compliance. Current guidelines recommend that combination pharmacotherapy might also be considered as initial treatment in patients with significant elevation of blood pressure and evidence of complications. Several effective and well-tolerated antihypertensive drug classes available today offer multiple options for combination therapy. The choice of antihypertensive agents should be made on the basis of current recommendations regarding first line drugs and compelling indications. Specific drug combinations might have additional beneficial or detrimental long-term metabolic effects, beyond their effects on blood pressure. However, more outcome data comparing antihypertensive drug combinations are required. The implementation of an intensive up-titration treatment strategy, together with a systematic use of full doses of multiple drug combinations, is expected to achieve optimal blood pressure control in the vast majority of hypertensive patients.     

Medikamentöse Therapie der gastroösophagealen Refluxkrankheit

Acid-suppressant drugs predominate in the treatment of gastroesophageal reflux disease. Proton pump inhibitors (PPI) are the first-line choice in both reflux esophagitis and nonerosive reflux disease (NERD). H(2)-blockers play a minor role and should not be used in erosive esophagitis. Other drugs such as mucosa-protective compounds, prokinetics, and antacids do not play a role, either alone oder in combination with acid suppressants. Proton pump inhibitors should also be used in maintenance therapy which is not associated with significant risks. There is a general trend toward on-demand treatment (already established in NERD). In cases refractory to therapy, the choice of drug should be critically analyzed (in case H(2)-blockers are used), and increasing the PPI dose is recommended; persistent symptoms should lead to reevaluation of the diagnosis. Asymptomatic Barrett's esophagus represents no indication for treatment, which in symptomatic patients is carried out in the normal fashion.     

The role of stereotactic biopsy in the management of HIV-related focal brain lesions.

The criteria for brain biopsy in patients with acquired immunodeficiency syndrome (AIDS) remain unclear and without universal acceptance. In order to shed more light on this issue, the authors reviewed the records of 25 AIDS patients with focal cerebral lesions who consecutively underwent stereotactic biopsy between November 1988 and October 1990. The most frequently occurring diagnoses were lymphoma (36%), progressive multifocal leukoencephalopathy (24%), and toxoplasmosis (8%). Patients whose central nervous system disease resulted in their initial presentation (approximately 40%) survived a median of 37 weeks, as opposed to 6 weeks for those who had previous AIDS-related infections. The proportion of biopsies of contrast-enhancing lesions that were diagnostic and thereby contributed to the patients' therapeutic management was 87.5%. On the other hand, only 67% of the biopsies of nonenhancing lesions were diagnostic, and none of these lesions were treatable. All of the lymphoma patients had had AIDS for some time and, despite a reasonable preoperative Karnofsky score and postoperative radiation therapy, their median survival was only 6 weeks; however, biopsy was critical to their therapeutic management. Early brain biopsy, rather than empiric antitoxoplasmosis therapy, appears indicated for aggressive therapy of contrast-enhancing lesions in patients who have had previous manifestations of AIDS. The role for biopsy of nonenhancing lesions is less clear, but it may provide prognostic information.     

Intracerebral mass lesions in patients affected by AIDS

Summary Toxoplasma gondii cerebral abscess is a common opportunistic infection in patients affected by AIDS. Making a reliable diagnosis of acute cerebral toxoplasmosis is difficult in AIDS patients because of the lack of specificity of serological data and neuroradiological findings. Brain biopsy is the only procedure which enables a reliable diagnosis to be made a trial of specific medical therapy for toxoplasmosis in patients affected by AIDS and intracranial mass lesion can be advisable before performing brain biopsy. The authors report the cases of three patients affected by AIDS and cerebral toxoplasmosis.Tissue diagnosis was made in the first patient from autopsy material while a presumptive diagnosis was made in the other two cases since specific medical therapy resulted in a dramatic improvement of the neurological status.Despite the good possibilities in the treatment of this complication AIDS, however, carries a poor prognosis.     

Schmerzsyndrome bei AIDS

Pain is a major, but largely neglected problem in AIDS patients. The aim of this article is to review the etiology of pain manifestations in AIDS patients in different organ systems and to discuss appropriate treatment strategies. The most common pain symptoms in AIDS patients are headache, oral cavity pain, dysphagia and adynophagia, chest pain, abdominal pain and pain related to peripheral neuropathy. Symptomatic pain treatment should be started while diagnostic work-up is still in progress, so that the patient does not suffer. If etiological treatment is possible, specific treatment should be started and symptomatic pain treatment tapered as tolerated. If etiological treatment is not possible, symptomatic pain treatment should be continued. In view of the multiple organs involved in the presentation of AIDS requiring multiple drugs, careful attention to side effects, contraindications and drug interactions is warranted, when administering pain medications. Fear of the complexity of these issues should, however, not prevent effective pain management for these patients, who suffer from a fatal disease. A multidisciplinary approach to painin AIDS patients, similar to the approach in patients with cancer, is desirable.     

Non-surgical treatment of tuberculomas of the brain

A personal series of 14 patients with tuberculomas of the brain were treated with anti-tuberculous drugs. There were eight patients with solitary and six with multiple lesions, the size of the lesions varying from 3 x 2 cm to 7.5 x 6 cm. The symptoms and signs of tuberculomas of the brain are non-specific. The initial diagnosis is therefore presumptive and based on their characteristic CT patterns on contrast enhancement. These patterns are usually solid enhancing lesions, ring enhancing lesions or mixed solid and ring forms. The final diagnosis is established by the patient's clinical improvement and the CT scan evidence of decrease in the extent of the oedema and the size of the lesion after a therapeutic test by means of triple anti-tuberculous drug therapy lasting for 12 weeks. All patients but one were treated successfully with triple anti-tuberculous drug therapy, for a continued total period of 18 months. A failure of medical treatment occurred in one patient due to non-compliance. In this patient, the residual cerebral lesion after the tuberculoma had healed required excision to control intractable epilepsy. Associated obstructive hydrocephalus in another patient needed a ventriculo-peritoneal shunt. The patients were followed for six months to five years. There were no recurrences. It is concluded that medical treatment with anti-tuberculous drugs is the treatment of choice for tuberculomas of the brain. With the use of steroids to control the brain oedema and its resultant mass effect and increased intracranial pressure, and a ventriculo-peritoneal shunt for hydrocephalus, almost all tuberculomas of the brain, irrespective of their size, can be cured by medical treatment.     

Treatment of anaphylactic reaction in pre-hospital and in the emergency room: literature review

Care and therapy of patients experiencing an anaphylactic reaction should be known by the physicians working in the emergency medical unit or in pre-hospital care. The epidemiology of these reactions varies according to the countries. The main aetiologies are due to food, hymenoptera or drugs. The clinical scale proposed by Ring and Messmer aims to classify the reactions in 4 grades according to their severity and is useful to stratify therapy. According to the grade of the reaction, the drug of choice for the treatment of anaphylaxis is epinephrine associated to vascular expansion. Anaphylaxis during pregnancy is described. Patients who experienced an immediate hypersensitivity reaction should undergo an allergological investigation to prove the immune mechanism and to identify the culprit allergen. Reporting to the Drug Safety Monitoring Authorities when a drug is implicated should not be forgotten.     

Acquired immunodeficiency syndrome and the kidney

Initial autopsy studies concerned primarily with the systemic manifestations of the acquired immunodeficiency syndrome (AIDS) did not indicate that significant renal problems were likely to occur in AIDS patients. However, several recent studies have suggested that important renal and electrolyte disorders develop frequently in at least some groups of AIDS patients. In this report, we review current information concerning such disorders and describe our study of the frequency and types of renal lesions in the first 50 AIDS patients undergoing autopsy at this institution. We conclude that a number of renal lesions and electrolyte abnormalities occur in AIDS patients, although the frequency and nature of these problems vary considerably from center to center. Studies from several centers, including our own, indicate that AIDS patients are particularly likely to develop tubulointerstitial lesions (such as nephrocalcinosis and interstitial nephritis) and electrolyte disorders. Additional studies from specific centers in New York City, Miami, Detroit, and Los Angeles indicate that AIDS patients can also develop glomerular lesions, including a variant of focal and segmental glomerulosclerosis (FSGS) associated with heavy proteinuria and rapidly progressive renal failure. Although FSGS is not commonly observed in all centers, AIDS patients with this lesion appear to have a distinctive combination of clinical and pathological features, suggesting that they have a specific "human immunodeficiency virus (HIV)-associated" nephropathy. Preliminary evidence suggests that this lesion may be related to direct renal HIV infection, although confirmation of this possibility is needed. The approach to the AIDS patient with renal disease should involve correction of reversible disorders and consideration of dialysis as necessary.     

Dietary and medicamentous therapy of chronic constipation]

Therapy of constipation is complex. It is mainly based on general rules and treatment with dietary fibers. If drugs are necessary they should be applied according to the type of constipation as evidenced by the results of special diagnostic procedures. Some patients may improve with psychotherapeutic procedures. Surgical treatment should be the last choice. The aim of therapy is to relieve the patient from his symptoms and achieve a habit of regular defecation, if possible with only a small amount of laxatives--or better without the application of drugs. Most often a highly individualized therapy is necessary. Many patients consult their doctor only when they have already a grave problem. Therapy then becomes difficult. Information on bowel movements and on how to prevent constipation by the way of living, therefore, should be widely spread in the general population in order to minimize constipation as a medical problem.     

Bladder carcinoma in situ in 2003: state of the art

Carcinoma is situ (CIS) of the bladder is a high-grade non-invasive malignancy with a high tendency of progression and transitional cell carcinoma outside the bladder. The diagnosis is a combination of abnormal cytology and cystoscopy with biopsies. Although cytology has clear limitations in low-grade lesions, such as a low inter- and intra-observer reproducibility, high-grade lesions and CIS should be diagnosed with a high degree of sensitivity and specificity. Currently available urinary markers do not (yet) seem to match cytology. The cystoscopic diagnosis is more difficult, since flat lesions are often difficult to see. The application of fluorescence cystoscopy and resection clearly improves the detection of the number of CIS lesions per patient and also the number of patients with CIS. For treatment of CIS (maintenance) BCG remains the golden standard. BCG appears to be able to prevent or delay progression to muscle invasive disease. BCG refractory patients are at high risk for progression and cancer death, and cystectomy is the treatment of choice. Alternatives for BCG refractory CIS patients, like intravesical chemo-immunotherapy, new chemotherapeutic drugs or photo-dynamic therapy, remain highly experimental. Last but not least, the danger for CIS patients is failure to respond to therapy and a high subsequent chance of progression and cancer-specific death. Unfortunately, despite much research, this prediction is not yet possible with molecular markers in daily practice.     

Influence of cause on choice of therapy in 174 patients with erectile dysfunction.

In 174 impotent patients consistent application of modern diagnostic methods, including dynamic color duplex sonography, pharmacocavernosography, nocturnal penile tumescence monitoring and psychological exploration, led to invasive therapy in 38 and to self-injection therapy in 76. Analysis of patients who received penile implants and those who performed self-injection did not show an important effect of etiology of impotence on the choice of treatment. Therefore, if penile vascular surgery is excluded, diagnostic procedures can be limited to a simplified goal-directed panel. Once psychogenic impotence is excluded through nocturnal penile tumescence monitoring, application of vasoactive drugs serves only to select patients to be considered for self-injection therapy. Implant surgery will be reserved for patients who fail to respond to any drug applied.     

Sulfadiazine-associated obstructive nephropathy occurring in a patient with the acquired immunodeficiency syndrome

A 45-year-old man with the Acquired Immunodeficiency Syndrome (AIDS) and CNS toxoplasmosis presented with acute renal failure, hematuria, and renal colic shortly after starting treatment with sulfadiazine. Ultrasound examination of his kidneys was suggestive of intraparenchymal crystallization of sulfadiazine. His renal failure and ultrasound findings rapidly resolved with alkaline hydration. On rechallenge with sulfadiazine, he again developed renal insufficiency and ultrasonic findings consistent with stones. The use of sulfadiazine in the treatment of CNS toxoplasmosis in AIDS patients should be monitored carefully with the recognition that this form of crystalline-induced acute renal failure can occur in a dehydrated patient.     

Surgery for hyperthyroidism: indications, pretreatment, operative strategy and results

In an endemic area nodular toxic goitre is the dominating type of hyperthyroidism, while Graves' or Basedow's disease with diffuse toxic goitre accounts for only 25 to 30% of the patients. Since antithyroid drug therapy has poor permanent effect and recurrence rates of about 50 to 60% and radioiodine in turn requires higher doses and often repeated application, surgery is to be recommended as the primary treatment of choice for the nodular hyperthyroid goitre. -For Graves' disease the method of therapy is not as clear cut. Operation is indicated mainly when the disease is severe with a larger goitre or in younger age groups (below 40 years) where radioiodine may not be advisable. For preoperative treatment the use of antithyroid drugs in preferred, although iodine perhaps in combination with beta blockers may be used safely as well at least for moderate cases. In the presence of alternative means of treatment surgery should not exceed an operative risk of 0.5-1.5% with virtually no mortality. Our own experiences are based on a retrospective analysis of 702 patients from three hospitals.