Detection of Borrelia burgdorferi sensu lato in lesional skin of patients with erythema migrans and acrodermatitis chronica atrophicans by ospA-specific PCR.

The aim of this study was to develop a sensitive and specific PCR for the detection of Borrelia burgdorferi DNA. The plasmid-located gene coding for the outer surface protein A (OspA [31-kDa protein]) was used as a target. Nucleotide sequence information from different B. burgdorferi ospA genotypes was used to design primers homologous to different genotypes. The sensitivity of the nested PCR differed from 1 fg to 1 pg of borrelial DNA, depending on the strain analyzed. No cross-reactions with DNA from spirochetes other than B. burgdorferi or with human DNA were observed. A total of 22 skin biopsy samples from patients with erythema migrans (EM [n = 10]) or acrodermatitis chronica atrophicans (ACA [n = 12]) were examined for the presence of B. burgdorferi by nested PCR. Of 22 biopsies, 80% from EM patients and 92% from ACA patients were positive by PCR amplification. By comparison, 50% of the EM patients had elevated B. burgdorferi-specific immunoglobulin M (IgM) and/or IgG antibody levels as tested by enzyme-linked immunosorbent assay (ELISA) using purified B. burgdorferi flagella as antigen. A total of 33% of ACA patients had elevated IgM titers, and all had high IgG titers in their sera. Only 30% of specimens from patients with EM and none from patients with ACA were positive by culture. All culture-positive specimens were also positive by PCR. Thus, the sensitivities of the PCR were 80 and 92%, respectively, for patients with EM and ACA on the basis of the clinical and histopathological diagnoses of Lyme disease. From these results, we conclude that PCR is a suitable method to detect B. burdorferi sensu lato DNA in skin biopsy samples and could be applied as an additional diagnostic tool.     

Focal pulmonary edema. Correlation with perfusion lung scan

Pulmonary embolism is diagnosed by a mismatched perfusion-ventilation lung scan. The probability is increased further when there is an associated "hot spot" in the perfusion study caused by focal pulmonary edema.     

Maintenance ECT: A Survey of Practice (1986)

A questionnaire on the use of maintenance or continuation ECT was mailed to 173 practitioners of ECT. Of 86 respondents, 51 reported they used maintenance therapy, and 35 did not. Users came from 24 states, with five states accounting for more than half. Of practitioners giving maintenance ECT, each treated a median of three patients annually between 1981 through 1984, with a range from zero to "thousands." Frequency of treatments is determined empirically, with most treatments given monthly. Memory impairment is the most commonly cited risk. Depression is the diagnosis in 90% of the patients, with schizoaffective, schizophrenic, and manic patients equally comprising the remainder of the patients. The longest series reported for any one patient is 2,400 treatments.     

Failure of misonidazole-sensitized radiotherapy to impact upon outcome among stage III-IV squamous cancers of the head and neck

As part of the RTOG research effort in the treatment of advanced, inoperable squamous cancer of the head and neck region, the hypoxic cell sensitizer, misonidazole, was selected for investigation as an adjuvant to definitive irradiation. Based upon a pilot experience (78-02) showing a 67% complete response rate among 36 AJC Stage III-IV patients receiving full-dose irradiation and 6 weekly p.o. doses of misonidazole, a phase III trial was carried out from '79-'83. Three hundred and six patients were entered, 42% of whom had oropharyngeal primaries and with 78% of all cases representing T3 or T4 (inoperable) lesions. Only 16% of the entire series presented with N0 necks. Fractionation was altered among the misonidazole-receiving patients, in contrast to "standard" 5 treatments per week among "control" patients, such that 2 separate treatments were given on each day of p.o. misonidazole administration (2.0 gm/m2/wk X 6 doses, 2.5 Gy in a.m., 2.1 Gy in p.m.). Total tumor doses were identical among the two treatment arms except that a limitation of 40.0 Gy to spinal cord was specified for sensitized radiotherapy vs. 45.0 Gy for "control" patients. Primary tumor clearance was observed to be 55-60%, with minor variations according to tumor stage and site. The local regional control rate among radiotherapy-alone patients was 26% at 2 years compared to 22% (2 years) within the misonidazole-receiving group. Analysis of survival revealed no advantage to the sensitized patients, with 55 +/- 2% surviving 1 year and 22 +/- 1% living 3 years following treatment in both treatment categories. Distant metastases as first site of failure (12-13%) and the local failure among initial complete responders (46%) showed no advantage to the misonidazole group. Although a misonidazole dosage of 2.0 gm/m2/wk X 6 (12 gm/m2 total) is well tolerated, no clinical benefit was demonstrated in this randomized trial. Other nitroimidazole analogs (e.g. SR-2508) are now being investigated.     

"Clear cell" atypical fibroxanthoma

An 87-year-old man with extensive solar damage presented with a 2-month history of a dome-shaped, crusted lesion on the dorsum of the left hand. Microscopically, the tumor consisted of fascicles of spindle cells with bizarre nuclei and clear, vacuolated cytoplasm. Histochemical, immunohistochemical, and ultrastructural features supported the diagnosis of atypical fibroxanthoma. There was no evidence of metastatic disease. The lesion was completely excised, and there has been no recurrence in 3 months of observation. This unusual "clear cell" variant of atypical fibroxanthoma must be distinguished from other clear cell tumors, such as metastatic renal cell carcinoma, clear cell eccrine carcinoma, and clear cell sarcoma (malignant melanoma) of soft parts. Although atypical fibroxanthoma is usually cured by complete surgical excision, metastases have been reported.     

Adult-onset autosomal dominant limb-girdle muscular dystrophy

We describe a kindred with a rare autosomal dominant myopathy limited to the limb-girdle muscles, beginning insidiously any time from the late second through the sixth decades and followed by slow progression. Pelvifemoral precedes scapulohumeral weakness, and proximal appendicular involvement antedates limited distal paresis. Expressivity varies and includes an asymptomatic myopathy (preclinical or subclinical) and a nonmanifesting carrier state that extends well into the eighth decade. A variety of nonspecific changes are present in muscle on light, enzyme histochemical, and electron microscopic examination; of these changes, "rimmed" or autophagic vacuoles are the most characteristic. We identified one very similar previously reported genealogy. The similarities between the two unrelated families clearly establish this dystrophic process as a distinct genetic entity; their differences suggest genetic heterogeneity.     

The Yale algorithm. Special workshop--clinical

The assessment of causality in drug-event associations depends on the setting and purpose of such an assessment. Epidemiologists are primarily interested in population-based inferences about whether a given drug can cause a certain adverse drug reaction (ADR), and if so, how often it does so. Pharmaceutical industries and regulatory agencies are also concerned with population-based risks, but in addition must worry about individual cases. Clinicians are primarily interested in the individual, ie, whether a given drug did cause a certain adverse event in a particular patient. The authors describe an algorithm that provides specific, detailed criteria for ranking the probability that an observed untoward clinical manifestation was caused by a given drug. The criteria are subdivided into six axes of decision strategy with a built-in scoring system that ordinally ranks the probability of an adverse drug reaction as definite, probable, possible, or unlikely. To illustrate the use of the algorithm, the authors assess a reference case of pancreatitis occurring after administration of methyldopa.     

Tula Virus as Causative Agent of Hantavirus Disease in Immunocompetent Person,Germany

We report molecular evidence of Tula virus infection in an immunocompetent patient from Germany who had typical signs of hantavirus disease. Accumulating evidence indicates that Tula virus infection, although often considered nonpathogenic, represents a threat to human health.     

Mathematical model of volume kinetics and renal function after burn injury and resuscitation

This paper presents a mathematical model of blood volume kinetics and renal function in response to burn injury and resuscitation, which is applicable to the development and non-clinical testing of burn resuscitation protocols and algorithms. Prior mathematical models of burn injury and resuscitation are not ideally suited to such applications due to their limited credibility in predicting blood volume and urinary output observed in wide-ranging burn patients as well as in incorporating contemporary knowledge of burn pathophysiology. Our mathematical model consists of an established multi-compartmental model of blood volume kinetics, a hybrid mechanistic-phenomenological model of renal function, and novel lumped-parameter models of burn-induced perturbations in volume kinetics and renal function equipped with contemporary knowledge on burn-related physiology and pathophysiology. Using the dataset collected from 16 sheep, we showed that our mathematical model can be characterized with physiologically plausible parameter values to accurately predict blood volume kinetic and renal function responses to burn injury and resuscitation on an individual basis against a wide range of pathophysiological variability. Pending validation in humans, our mathematical model may serve as an effective basis for in-depth understanding of complex burn-induced volume kinetic and renal function responses as well as development and non-clinical testing of burn resuscitation protocols and algorithms.