Late postpartum eclampsia at five weeks post-delivery

Postpartum eclampsia is a serious and unexpected complication. A relative increase in the incidence of postpartum eclampsia has been noted in the last few years. Late postpartum eclampsia, though initially controversial, is now recognised up to four weeks after delivery. We present such a case occurring in a 26-year-old woman. This patient, who had undergone lower segment caesarean section due to pregnancy-induced hypertension, presented with typical features of postpartum eclampsia 34 days after an asymptomatic interval.     

What is the dosimetric impact of isotropic vs anisotropic safety margins for delineation of the clinical target volume in breast brachytherapy?

PurposeThe purpose of the study was to report dosimetric differences for breast brachytherapy plans optimized for clinical target volume (CTV) generated using conventional isotropic expansion of tumor bed volume (TBV) and Groupe Européen de Curiethérapie–European Society for Radiotherapy and Oncology (GEC-ESTRO) recommendations to expand the TBV anisotropically to achieve a total safety margin of 2 cm (resection margin size + added safety margin).MethodsInstitutional records of 100 patients who underwent accelerated partial breast irradiation using multicatheter interstitial brachytherapy from May 2015 to March 2020 were reviewed retrospectively. Two sets of CT-based plans were made, one with 1-cm isotropic margins around the tumor bed (CTV_ISO) and the other with anisotropic margins (CTV_GEC). Plans were evaluated and compared using the American Brachytherapy Society and GEC-ESTRO guidelines.ResultsThe median TBV was 36.97 cc. The median margin widths were as follows: anterior 1.2, posterior 1.0, superior 1.0, inferior 0.9, medial 1.2, and lateral 1.2 cm. The mean tumor bed coverage index was 0.94; 0.93 [p.066], the CTV coverage index 0.86; 0.84 [p 0.001], the dose homogeneity index (DHI) 0.77; 0.75 [p < 0.001] and the conformity index 0.66; 0.64 [p < 0.001] in CTV_ISO and CTV_GEC plans, respectively. In smaller volume implants (TBV< 35 cc), the DHI was 0.76; 0.75 [p 0.008] and the conformity index was 0.66; 0.62 [p < 0.001], whereas in larger volumes >35 cc, the CTV coverage index was 0.86; 0.84 [p 0.003] and the DHI 0.78; 0.76 [p 0.001] in CTV_ISO and CTV_GEC plans, respectively.ConclusionsIn this cohort of patients who underwent accelerated partial breast irradiation, plans with anisotropic margins had lower conformity, the impact of which was predominantly seen in smaller implants. Rest of the dosimetric constraints were achieved in both the plans as per the American Brachytherapy Society and GEC-ESTRO guidelines.     

Lipomatous variant of angiomyofibroblastoma: a case report and review of the literature

Angiomyofibroblastoma represents a rare, benign mesenchymal tumor with a predilection for the vulvovaginal region. Lipomatous change may occur but rarely comprises a substantial component of the lesion. There are only eight reports in the English language literature describing the lipomatous variant of this tumor. We describe a further lipomatous angiomyofibroblastoma that occurred on the labium majus of a 49‐year‐old woman. The histopathologic and immunohistochemical features are described, and the collective experience in the literature is reviewed.     

Effect of rifampicin on the pharmacokinetics and pharmacodynamics of saxagliptin, a dipeptidyl peptidase-4 inhibitor, in healthy subjects

AIM

To investigate the effect of co-administration of rifampicin, a potent inducer of cytochrome P450 (CYP) 3A4 enzymes, on the pharmacokinetics (PK) and pharmacodynamics (PD) of saxagliptin and 5-hydroxy saxagliptin in healthy subjects. Saxagliptin is metabolized by CYP3A4/3A5 to 5-hydroxy saxagliptin, its major pharmacologically active metabolite.

METHODS

In a non-randomized, open label, single sequence design, 14 healthy subjects received single oral doses of saxagliptin 5 mg with and without steady-state rifampicin (600 mg once daily for 6 days). PK (saxagliptin and 5-hydroxy saxagliptin) and PD (plasma DPP-4 activity) were measured for up to 24 h on days 1 and 7.

RESULTS

Concomitant administration with rifampicin resulted in 53% (point estimate 0.47, 90% CI 0.38, 0.57) and 76% (point estimate 0.24, 90% CI 0.21, 0.27) decreases in the geometric mean C_max and AUC values of saxagliptin, respectively, with a 39% (point estimate 1.39, 90% CI 1.23, 1.56) increase in the geometric mean C_max and no change (point estimate 1.03, 90% CI 0.97, 1.09) in the AUC of 5-hydroxy saxagliptin. Similar maximum % inhibition and area under the % inhibition−time effect curve over 24 h for DPP-4 activity were observed when saxagliptin was administered alone or with rifampicin. The saxagliptin total active moieties exposure (AUC) decreased by 27% (point estimate 0.73, 90% CI 0.66, 0.81). Saxagliptin with or without rifampicin in this study was generally well tolerated.

CONCLUSIONS

Lack of change of PD effect of saxagliptin is consistent with the observed 27% reduction in systemic exposure to the total active moieties, which is not considered clinically meaningful. Based on these findings, it is not necessary to adjust the saxagliptin dose when co-administered with rifampicin.     

High Resolution Computed Tomography in Stapedial Otosclerosis

The value of high-resolution CT scanning in diagnosing stapedial otosclerosis and in influencing surgical planning was studied. 40 cases, consisting of patients of both genders, above the age of 14 years, with a clinical diagnosis of otosclerosis underwent HRCT of the temporal bones. Images were acquired in axial plane, with a bone algorithm, keeping slice thickness at 0.5 mm and intervals of 0.5 mm. Reconstruction of the volume data set was done to obtain overlapping slices in various planes, so as to obtain the best possible images of the footplate of stapes. The thickness of the footplate was measured and the site of lesion was noted in these images. On exploratory tympanotomy, the footplate was assessed and graded according to a visual scale. HRCT was able to diagnose stapedial otosclerosis in 85% ears. It was able to identify the presence of a thickened footplate correctly with a sensitivity of 85.3% (P value 0.16). It was able to correctly localize the site of otosclerotic focus in 85% cases (P value <0.01). Thus, an estimate of the thickness of the footplate likely to be encountered and thus the amount of drilling likely to be required to create a fenestra; and the likely site of maximum thickness could be made pre-operatively. This study also established the value of multislice CT on the acquisition of such data. This method obviates the requirement of difficult patient positioning, reduces scanning time; while greatly improving the sensitivity of the scanning.     

Spectrum of neurological manifestations of idiopathic hypoparathyroidism and pseudohypoparathyroidism

We describe clinical, biochemical, radiological profile, and treatment outcome in 97 patients with idiopathic hypoparathyroidism seen over a period of 18 years. Of the 97 patients, 78 (80%) had idiopathic hypoparathyroidism and 19 (20%) had pseudohypoparathyroidism. The mean age±standard deviation (SD) at presentation was 28.7±14.1 years. There were 52 males, the mean lag time from first reported symptom to diagnosis was 5.9±5.2 years and the mean (±SD) follow-up was 1.8±0.4 years. The most common presenting manifestation was carpopedal spasm in 68 (70%) patients, followed by paresthesia and seizures in 52 (54%) patients. The mean (±SD) serum calcium and inorganic phosphate concentrations were 6.1±1.5 mg/dl and 6.3±1.5 mg/dl, respectively. The most common imaging abnormality noted was basal ganglia calcification followed by cerebral cortex and cerebellum calcification. More than one-third of patients were on various antiepileptic drugs including phenytoin. In addition to oral calcium and active vitamin D (calcitriol), twenty-six patients (27%) also required hydrochlorothiazide. The important finding in our study was long lag time from the first reported symptom to diagnosis. Phenytoin was the drug in almost one- third of our patients with seizures. Practicing clinicians should have high index of suspicion of diagnosis hypoparathyroidism in the appropriate clinical states to avoid the morbidity associated with hypoparathyroidism. Phenytoin should be avoided in patients with hypoparathyroidism and seizures.     

Key role for Bak activation and Bak-Bax interaction in the apoptotic response to vinblastine

Microtubule inhibitors such as vinblastine cause mitotic arrest and subsequent apoptosis through the intrinsic mitochondrial pathway. However, although Bcl-2 family proteins have been implicated as distal mediators, their precise role is largely unknown. In this study, we investigated the role of Bak in vinblastine-induced apoptosis. Bak was mainly monomeric in untreated KB-3 cells, and multimers corresponding to dimer, trimer, and higher oligomers were observed after vinblastine treatment. The oligomeric Bak species were strongly diminished in cells stably overexpressing Bcl-xL. Immunoprecipitation with a conformation-dependent Bak antibody revealed that vinblastine induced Bak activation. Reciprocal immunoprecipitations indicated that vinblastine induced the interaction of active Bak with active Bax. Furthermore, Bcl-xL overexpression prevented Bak and Bax interaction and strongly inhibited apoptosis, whereas Bcl-2 overexpression did not prevent Bak-Bax interaction and only weakly inhibited apoptosis. The relative contributions of Bak and Bax were investigated using fibroblasts deficient in one or both of these proteins; double knockouts were highly resistant compared with single knockouts, with vinblastine sensitivities in the order of Bak(+)/Bax(+) > Bak(+)/Bax(-) > Bak(-)/Bax(+) > Bak(-)/Bax(-). These results highlight Bak as a key mediator of vinblastine-induced apoptosis and show for the first time activation and oligomerization of Bak by an antimitotic agent. In addition, our results suggest that the interaction of the activated forms of Bak and Bax represents a key distal step in the apoptotic response to this important chemotherapeutic drug.     

Chromoblastomycosis in India

Background Chromoblastomycosis is reported for the first time from the states of Jammu-Kashmir and Bihar along with two additional cases from the stales of Assam and Uttar Pradesh. The work carried out on this disease in the Indian subcontinent is reviewed. Methods Relevant mycologic investigations, including direct microscopy, histopathology, and culture, were carried out of study the four cases. Treatment was given to two patients. Results The duration of the lesions varied from 5 to 32 years. In one case the lesion was a large erythematous plaque on the buttocks extending to the backs of the thighs, and in the others they were hypertrophic lesions on the extremities. Histopathologic study of specimens carried out in three patients revealed the causative organisms. On culture, Cladosporium carrionii was isolated in one and Fonsecaea species in the other three. The lesions in one patient were surgically excised and another patient responded well of a combined regimen of amphotericin B and 5-fluorocytosine. Conclusions Although chromoblastomycosis is widely distributed in India, many patients remain undiagnosed due to a lack of proper facilities. Treatment is difficult and most patients are not able to afford the drugs prescribed for this condition.