Is there a diurnal pattern in the clinical symptoms of HELLP syndrome?

OBJECTIVE: To determine if there is a diurnal pattern in the clinical symptoms of HELLP (Hemolysis, Elevated Liver enzymes, Low Platelets) syndrome. STUDY DESIGN: A retrospective study was performed in 134 pregnancies complicated by HELLP syndrome. The medical records were reviewed to describe each HELLP episode. Time of day was divided into three periods, day, evening, and night. The following parameters were categorized according to the time of day: onset of symptoms, consultation by the doctor, initial blood sampling, diagnosis and decrease of symptoms. Biochemical parameters at clinical presentation and consecutive changes within 24 h were recorded. RESULTS: In 65 pregnancies 77 HELLP episodes were well documented. Times of onset of symptoms and consultation by the doctor were significantly higher during the evening and night (p < 0.001), whereas times of diagnosis and decrease of symptoms occurred significantly more during the day (p < 0.001). In only 49.3% of the cases were diagnostic laboratory criteria met at clinical presentation. This was mainly due to platelet values in excess of 100 x 10(9)/l. Several hours later (median 8 h, range 2-23) the decrease in platelets occurred. CONCLUSIONS: A diurnal pattern exists in the clinical symptoms of HELLP syndrome that is characterized by an exacerbation during the night and recovery during the day. There is a considerable delay between the onset of symptoms and the fulfillment of diagnostic laboratory criteria.     

Immunocryosurgery for basal cell carcinoma: results of a pilot, prospective, open-label study of cryosurgery during continued imiquimod application

Background/aim  Theoretical considerations support the combination of cryosurgery and topical imiquimod to treat basal cell carcinomas (BCC). The aim of the present study was to test the feasibility and efficacy of 'cryosurgery during continued imiquimod application' ('immunocryosurgery') to treat 'high-risk-for-recurrence' BCCs.
Methods  Thirteen patients with 21 biopsy-proven tumours (4 of 21 relapses after prior surgery) were included. After 2–5 weeks (median, 3) of daily 5% imiquimod cream application, the tumours were treated by liquid N₂ cryosurgery (spray, two cycles, 10–20 s) and imiquimod was continued for additional 2–12 weeks (median, 4). The outcome after at least 18 months of follow-up (18–24 months) is currently reported.
Results  Nineteen of 21 tumours responded promptly to immunocryosurgery; two tumours required additional treatment cycles to clear. Thus, the clinical clearance rate was 100%. Only 1 of 21(5%) tumour relapsed after at least 18 months of follow-up (cumulative efficacy: 95%).
Conclusions  'Immunocryosurgery' is a promising non-surgical combination modality to treat 'high-risk-for-recurrence BCCs'. Initial evidence is suggestive of an at least additive effect of the two combined modalities. Further studies comparing immunocryosurgery directly with cryosurgery and imiquimod monotherapies will confirm the reported results.     

Comorbidity and social phobia: evidence from clinical,epidemiologic, and genetic studies

This paper reviews evidence from clinical, epidemiologic, and family studies regarding the association between social phobia and other syndromes. Social phobia is strongly associated with other anxiety disorders, substance abuse, and affective disorders in both clinical and community samples. An average of 80% of social phobics identified in community samples meet diagnostic criteria for another lifetime condition. Social phobia is most strongly associated with other subtypes of anxiety disorders, with an average of 50% of social phobics in the community reporting a concomitant anxiety disorder including another phobic disorder, generalized anciety, or panic disorder. Approximately 20% of subjects in the community meet lifetime criteria for a major depressive disorder. The onset of social phobia generally precedes that of all other disorders, with the exception of simple phobia. Both clinical severity and treated prevalence are consistently greater among social phobics with comorbid disorders The results of family and twin studies reveal that shared etiologic factors explain a substantial proportion of the comorbidity between social phobia and depression, whereas the association between social phobia and alcoholism derives from a nonfamilial causal relationship between the two conditions. Clinical and phenomenologic implications of these findings are discussed.     

The bioavailability and nonlinear pharmacokinetics of MK-679 in humans

MK-679 (R(?)-3-((3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)(3-(dimethylamino)-3-oxopropyl)thio)methyl)thio(propanoic acid) is a potent and specific LTD₄-receptor antagonist. The disposition of MK-679 was investigated in a three-way crossover study in 12 healthy males receiving single intravenous doses of 75, 250, and 500 mg of MK-679. A greater than proportional increase in the area under the plasma concentration—time curve of MK-679 was observed with increase in dose. The plasma concentration data for each subject fitted well to the differential equations for a two-compartment model with linear tissue distribution and Michaelis-Menten elimination from the central compartment, indicating that the elimination of MK-679 in humans is saturable. In a previous study, the disposition of MK-679 in humans was also dose-dependent when given together with its S(+)-isomer, L-668,018. Thus, the disposition of MK-679 in humans is dose-dependent regardless of the presence of its stereoisomer. Also, the bioavailability of MK-679 was determined in six healthy males receiving simultaneously an oral dose of 250 mg of MK-679 and intravenous infusion of 1 mg ¹⁴C-MK-679. Results of this study indicate that the oral bioavailability of MK-679 is nearly quantitative.     

Risk factors associated with venous thromboembolic events in patients with malignancy.

Malignancy is a major risk factor for venous thromboembolic events, but not all patients with malignancy develop such events. This study attempts to identify risk factors in patients with malignancy who develop venous thromboembolic events. In the current study, 566 consecutive patients without venous thromboembolic events and 416 patients with, admitted to University of Michigan with malignancy between 1992 and 2000, were identified using International Classification of Diseases-9 Clinical Modification codes. Data on potential risk factors was obtained from the University of Michigan Cancer Registry and the medical record. Univariate and multivariate analysis was used to identify factors associated with venous thromboembolic events and mortality. The mean patient age was 45.6 years with a mean survival of 7.8 years from cancer diagnosis. Venous thromboembolic events were associated with solid tumors (odds ratio 5.0; 95% confidence interval 1.7-14.9; P = 0.004), infection (4.9; 1.2-19.8; P = 0.03), and increasing age (1.05; 1.03-1.08; P < 0.001). While leukopenia (4.2; 1.2-14.6; P = 0.02) was associated with an increased incidence of venous thromboembolic events, neutropenia was not. Sex, type of therapy, and cancer stage were not independently associated with venous thromboembolic events. Survival was decreased in patients with venous thromboembolic events (5.9 versus 9.2 years, P < 0.0001). Solid tumors (3.9; 1.8-8.4; P = 0.001), infection (3.3; 1.1-9.9; P = 0.03), advanced stage (1.6; 1.2-2.1; P = 0.001), and increasing age (1.02; 1.0-1.04; P = 0.01) were associated with decreased survival. Patients with malignancy who have solid tumors, advanced age, infection, and leukopenia have a significantly increased risk of venous thromboembolic events.     

Neuroleptic malignant syndrome

While on holiday in Zimbabwe, a forty-one year old woman with a long history of intermittent psychiatric illness developed what was diagnosed as neuroleptic malignant syndrome. She was admitted to the Intensive Care Unit of Harare Central Hospital and was treated successfully with bromocriptine and dantrolene.     

Uroscopy in the 21st century: high-field NMR spectroscopy

From the experiments described, it can be seen that there are different research approaches that can be taken and these are summarized in Table 1. Whereas much scientific research is principally hypothesis led, there remains, nevertheless, an important place for exploratory research. High resolution NMR can measure, directly and simultaneously, a wide range of endogenous metabolites in biological fluids and has the unique capability of providing structural information on the metabolites detected. It has proved to be a powerful research tool with which to study inherited metabolic diseases, renal disease, drug metabolism, and toxicity, and can be used to monitor the effects of drug therapy. For instance, by using a library of experimental toxins one can map the metabolic profile of site-specific nephron injury. With this approach in man one could eventually take an unknown disease such as Balkan nephropathy and predict the initial site of tubular injury, the mode of injury and therefore the kind of toxin capable of producing that injury. NMR spectroscopic techniques are still advancing rapidly, with ever increasing sensitivity and sophistication of NMR pulse sequences to enhance structural elucidation in complex mixtures. Given the advances in directly coupled HPLC-NMR and even HPLC-NMR-mass spectroscopy it is likely that these technologies in conjunction with pattern recognition will make major contribution to our understanding of renal processes and provide new diagnostic insights in the 21st century.      

Surgical treatment of Pancoast tumours.

Due to its localisation in the apex of the lung with invasion of the lower part of the brachial plexus, first ribs, vertebrae, subclavian vessels or stellate ganglion, a superior sulcus tumour causes characteristic symptoms, like arm or shoulder pain or Horner's syndrome. If rib invasion is the only feature, lysis of the rib must be evident on the chest radiograph; otherwise the tumour cannot be defined as a Pancoast tumour. It is important to adequately stage the tumour, because staging significantly influences survival. Survival is better for T3 than T4 tumours and mediastinal lymph node involvement has been found to be a negative prognostic factor. Also Horner's syndrome and incompleteness of resection worsen survival. The management of superior sulcus tumours has evolved over the past 50 years. Before 1950 it was considered to be inoperable and uniformly fatal. Shaw and Paulson introduced combined modality treatment and for many years, this combination of radiotherapy and surgery was the treatment of choice with a mean 5-year survival of approximately 30%. Postoperative radiotherapy or brachytherapy does not improve survival in patients with complete or incomplete resection. The tumour can be resected through the classic posterior Shaw-Paulson approach or the newer anterior transcervical approach, introduced by Dartevelle. This method facilitates better exposure of the extreme apex of the lung, brachial plexus and subclavian vessels. Regarding the extent of pulmonary resection, en bloc resection of the involved ribs with a lobectomy is recommended. Recent multimodality studies, involving chemoradiotherapy and surgical resection, show promising results regarding completeness of resection, local recurrence and survival, provided that appropriate staging has been carried out. However, careful patient selection and adequate perioperative management with protection of the bronchial stump or anastomosis are important to achieve reasonable rates of morbidity and mortality. As brain metastases remain one of the most common forms of relapse, further studies are needed to examine the role of prophylactic cranial irradiation in patients with complete resection. Also the addition of other chemotherapy agents or biologic agents such as angiogenesis inhibitors or tyrosine kinase inhibitors gives a new perspective in the treatment of Pancoast tumours.