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In idiopathic thrombocytopenic purpura, a known immune-mediated disorder, intravenous IgG is the treatment of choice. Success and the lack of side effects of intravenous IgG in the treatment of idiopathic thrombocytopenic purpura have encouraged consideration of its use in the treatment of neurologic disorders of presumed autoimmune pathogenesis. In this report, we describe two patients who developed acute renal failure following intravenous IgG treatment. The first patient had chronic inflammatory demyelinating polyneuropathy and was treated with intravenous IgG instead of prednisone because of preexisting diabetes. The second patient had idiopathic thrombocytopenic purpura and received intravenous IgG treatment as part of standard care. The patient with idiopathic thrombocytopenic purpura had unrelated bilateral high-grade renal artery stenosis. Both patients had a creatinine level of 140 mumol/L (1.6 mg/dL) prior to treatment. Renal biopsies performed during acute renal failure in each patient demonstrated marked swelling and vacuolization of the proximal tubular epithelial cytoplasm typical of high-solute-load-induced damage (similar to that associated with the use of mannitol). This report draws attention to the importance of screening for impaired renal function before intravenous IgG therapy is initiated. The patients we describe received standard doses of intravenous IgG at the recommended infusion rate yet developed oliguric renal failure. Awareness of serious side effects and recognition of predisposing factors provide means of avoiding known life-threatening complications of intravenous IgG therapy.

Fine needle aspiration specimens from 29 patients with bone and soft tissue neoplasms were analyzed by flow cytometry for DNA index and cell cycle analysis to determine whether such studies were helpful in cytologic diagnosis. Of 15 cases initially cytologically diagnosed as benign, 14 had a DNA index of 1.0, indicating a diploid population. The remaining case diagnosed as cytologically benign had a DNA index of 1.3. Further tissue from this tumor revealed an osteogenic sarcoma. Of the 14 cases initially diagnosed as malignant, 12 were hyperdiploid. Cell cycle analysis showed that malignant tumors had a higher proportion of cells in S phase (15.2% +/- 8.7%) than benign tumors (6.9% +/- 1.6%). Furthermore, high-grade malignancies had a significantly greater number of cells in S phase (18.5% +/- 1.5%) than low-grade tumors (9.9% +/- 6.3%).

Twenty-five patients with soft tissue sarcomas were treated with Ir192 implants following wide local excision at our institution between 1982 and 1987. External beam radiotherapy was given in addition to the implant in a majority of patients. The median follow-up in these 25 patients is 36 months (12 to 75 months). Twenty patients have had no evidence of local recurrence following their primary treatment (FFR = 80%). A multivariate analysis using stepwise logistic regression was used to predict failure in 3 years or less. Potential predictors examined included age, sex, tumor location, primary versus recurrent disease, grade, histology, surgical margins, implant only versus implant plus external beam, and a ratio of the volume of tissue which received 65 Gy (TV65) to the tumor volume (TV), that is (TV65/TV). The single variable which was significantly associated with local failure by 3 years was a TV65/TV of less than one. Once this variable was entered into the analysis, no other factor proved statistically significant. Our data suggest that when attempting local control of soft tissue sarcomas with brachytherapy, the volume of tissue receiving 65 Gy (TV65) from both implant and external beam must exceed the volume of the excised lesion (TV). Since the volume of a tumor can be readily determined prior to surgical excision either by CT or MRI scanning, pre-planning of the implant volume could potentially reduce the rate of local failure.

The problem addressed was whether a research-based protocol on oral temperature measurement could be developed and used in the practice setting. The first phase of the study proposed to (a) identify research articles related to the subject; (b) evaluate the quality of the research; (c) assess the adequacy of the research base; and (d) select areas for future study. The results indicated that further clinically-based studies are needed before a protocol can be designed and tested in clinical practice.

In 13 women with premature follicular depletion (PFD) the concentration of T and B lymphocytes, T-cell subpopulation, and serum immunoglobulins was determined. Intending to study only women where no obvious cause for PFD existed, including autoimmune disease, five women were excluded because of significant titers of microsomal antibodies or antinuclear antibodies. In the remaining eight women a reduction in the percent of OKT4 (helper) lymphocytes (42.8 +/- 66 vs 50.7 +/- 3.7, P less than 0.005), the ratio of OKT4/OKT8 (suppressor/cytotoxic) lymphocytes (0.96 +/- 0.27 vs 1.6 +/- 0.25, P less than 0.001), and serum concentration of IgA (124 +/- 53 vs 210 +/- 81.5 mg/dl, P less than 0.01) were found compared to a control population. The concentration of T and B lymphocytes, IgG, IgM, and the cutaneous reactivity to mumps and candida antigens were similar in the two populations. It is hypothesized that a mild immune deficiency may predispose to PFD.

Clinically, patients with extraarticular synovial chondromatosis are seen with a juxtaarticular mass due to metaplasia of synovial cells and subsequent formation of cartilaginous nodules. Three patients are described to illustrate the varied clinical and radiographic features of this disease. One patient had involvement of the knee and wrist while another had involvement of the knee along with presumed intraarticular synovial chondromatosis of the elbow. The third patient had a solitary finger lesion. Routine radiographs in extraarticular synovial chondromatosis demonstrate either solitary or multiple calcified juxtaarticular masses with chondroid matrix. Bone scintigraphy reveals intense radionuclide uptake within the calcified masses. Computed tomography clearly defines the extent of the lesion. Arthrography can evaluate for intraarticular extension.

A woman with autoimmune oophoritis was found to have luteal phase progesterone levels throughout a six-month period of amenorrhea. The common presentation of amenorrhea or metrorrhagia, despite the presence of a corpus luteum, in women with autoimmune oophoritis might result from this chronic progesterone production. A clinical picture consistent with a persistent corpus luteum may be a very early sign of autoimmune oophoritis.

The way future pathologists are educated will change greatly, the author says. Though there is danger in what is to come, there are opportunities as well, and the author remains optimistic. In this article he explains why.

The effect of open mouth breathing, tachypnea, and hyperpnea, either alone or in combination, on sublingual and tympanic membrane temperature in healthy adults was investigated. Seventy-eight subjects maintained randomly assigned breathing patterns for 15 minutes. Temperatures were monitored immediately prior to and for 5 minutes following the breathing protocol. The only statistically significant finding (p less than .01) was a lower sublingual temperature with open mouth breathing. No significant changes in tympanic membrane temperature were seen.

This study was designed to evaluate the effects of the beta 1-selective adrenoceptor antagonist bisoprolol on blood pressure, heart rate, plasma catecholamines, platelet aggregation, and alpha 2- and beta-adrenoceptor density in 45 male hypertensive patients (WHO stages I-II). Following a two-week placebo phase, the patients received either 5, 10, or 20 mg bisoprolol in a double-blind randomized fashion, once daily for 12 weeks. On days - 14, 0, 1, 7, 28, 56, 84, and 1 and 2 weeks after discontinuation of treatment (administration of placebo), blood pressure and heart rate were measured in the supine and sitting position, as well as during and after a 15-min exercise period on a bicycle ergometer. Simultaneously with the hemodynamic measurements, blood samples were obtained for the determination of plasma catecholamines. Blood samples for the assessment of beta-receptor density on lymphocytes and alpha 2-receptor density on thrombocytes, as well as thrombocyte aggregation sensitivity, were collected before bicycle ergometry. Five, 10, and 20 mg bisoprolol caused dose-dependent reductions of blood pressure and heart rate at rest and at peak exercise. The responder rates (diastolic BP less than or equal to 90 mm Hg) were 33%, 67%, and 100% with 5, 10, and 20 mg bisoprolol, respectively. After discontinuation of active treatment, blood pressure and heart rate gradually returned to pretreatment values within 1-2 weeks. Plasma epinephrine and norepinephrine levels in patients in the supine position remained unchanged during the whole course of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

The ocular and systemic disposition of levobunolol (LBUN), an antiglaucoma agent, was studied in albino rabbits. After topical administration to eyes, LBUN was rapidly adsorbed, with 2.5% of the dose bioavailable to the intraocular tissues as intact drug and 46% to the systemic circulation. On passage across the cornea, approximately 4.7% of a topically applied LBUN dose was biotransformed to dihydrolevobunolol (DHB), and subsequently became bioavailable to intraocular tissues. The major sites of ocular metabolism were the cornea epithelium and the iris-ciliary body. Another 12% of the topical LBUN dose entered the systemic circulation as DHB after presystemic biotransformation. Our study indicated a rapid absorption of LBUN into the aqueous humor after topical dosing. The tpeak was 15 min after dosing and the Cmax was 4 micrograms/mL. Dihydrolevobunolol (DHB) was formed steadily and reached a maximum in the aqueous humor 45 min after dosing. After distribution equilibrium had been reached, the aqueous humor concentrations of both LBUN and DHB declined. Six hours after dosing, the concentration of DHB in the aqueous humor was approximately 10 times higher than that of its parent compound. Because DHB is equivalent to its parent compound in beta-blocking activity, its formation in the rabbit eye may contribute to the pharmacodynamic effects observed after topical doses of LBUN.

Scar formation after laminectomy was evaluated in dogs treated with hemostatic agents, antiinflammatory drugs, or mechanical barriers. Microfibrillar collagen was found to be superior to gelatin foam. The antiinflammatory drugs delayed healing and frequently resulted in abscess formation, and eventually scar filled the defect. The fat grafts formed a viable mechanical barrier. Gelatin foam sponge was compared with microfibrillar collagen for hemostasis with free fat grafts in a clinical series of 50 patients. The latter technique was clearly superior.

A preliminary study demonstrated intracytoplasmic polyvalent immunoglobulin in human pleural fluid cells using a direct immunofluorescence technique. Of 33 pleural-fluid cell samples tested, 31 contained cells that initially stained positive for polyvalent immunoglobulin. The two negative specimens were from malignant effusions. Eleven of the specimens were cultured for seven days; nine of the eleven cultured specimens tested negative for polyvalent immunoglobulin after four days in culture. The remaining two specimens showed a marked decrease in positivity. After adding cell-free pleural fluid to the cultures on day four, the nine negative samples became positive again by day seven; the two slightly positive cases became strongly positive. The significance of these findings is discussed.

The study was designed to follow the haemodynamic effects and pharmacokinetics under steady-state conditions of three different doses of urapidil infused continuously. Nine male hypertensive patients received three randomly assigned intravenous infusions of 32.5, 65 and 130 mg urapidil, over 14 h during 6 consecutive days, in a change-over fashion. Blood pressure and heart rate were measured over a period of 28 h after the infusion began and were compared with a reference profile obtained prior to the treatment periods. Urapidil and its main metabolite, parahydroxylated urapidil, were also determined for 28 h after the infusion began using HPLC. The 32.5 mg dose of urapidil caused a maximum decrease in systolic blood pressure of 33 +/- 8 mmHg, the 65 mg dose a maximum decrease of 39 +/- mmHg and the 130 mg dose a maximum decrease of 50 +/- 12 mmHg. The 32.5 and 65 mg doses resulted in similar serum urapidil concentrations, with maximum levels in the 100 to 200 ng/ml range, and the 130 mg dose caused a maximum level approximately four times that achieved with the 32.5 mg dose. The serum concentration of parahydroxy urapidil was proportional to the corresponding dose of urapidil. Four patients reported mild headache, fatigue, weakness, pressure in the head, perspiration and orthostatic dysregulation. The side-effects were probably drug related but required no specific therapy. In summary, the 32.5 mg dose of urapidil resulted in a pronounced decrease in blood pressure. The average pressure reduction over the 14-h infusion period showed further dose-dependent increases after the 65 and 130 mg doses.(ABSTRACT TRUNCATED AT 250 WORDS)

The percutaneous absorption and distribution profile of hexamethylene lauramide (hexahydro-1-lauroyl-1H-azepine) were examined using a rat skin-flap model. After a topical dose to the skin flap, the drug concentrations in the vasculature at the site of drug application and in the systemic blood were monitored simultaneously. Hexamethylene lauramide penetrated the skin and reached a steady state in stratum corneum, viable epidermis, dermis, and cutaneous blood in 3 hr. Its concentration in the skin was much higher than that in the blood. Its apparent concentration in the epidermis was 19 times that in the dermis and about 3000 times that in the cutaneous blood. The percutaneous absorption of 14C-hexamethylene lauramide resulted in ascending systemic blood concentrations throughout the experimental period, whereas the cutaneous blood levels remained steady. The topically absorbed hexamethylene lauramide was quantitatively recovered in urine (85%) and feces (13%). The half-lives of urinary and fecal excretion of 14C-hexamethylene lauramide were 17 and 30 hr, respectively. Hexamethylene lauramide, when topically coadministered in an experimental formulation, enhanced the skin penetration of hydrocortisone with increased drug contents in the stratum corneum (2-fold) and with increased hydrocortisone concentrations in the cutaneous blood (3.4-fold) and the systemic blood (3.5-fold). The results indicated that the high concentration and retention of hexamethylene lauramide in stratum corneum and viable epidermis may contribute to its penetration enhancement effect in the skin. A steady state in percutaneous tissues was observed before the drug reached distribution equilibrium systemically. The systemic blood concentration of a topically applied agent therefore may not reflect its percutaneous kinetic processes before a systemic distribution equilibrium is reached.(ABSTRACT TRUNCATED AT 250 WORDS)