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R Chatterjee

Publications and source records attributed to R Chatterjee.

At least 19 recordsLinked to original sources
PubMed2003

Germ cell damage and Leydig cell insufficiency in recipients of nonmyeloablative transplantation for haematological malignancies.

Most bone marrow transplant recipients are infertile due to reversible or irreversible testicular failure. However, little is known about the gonadotoxic potential of the newly introduced nonmyeloablative transplants. We undertook a 24-month longitudinal study in a cohort of 32 recipients of nonmyeloablative transplantation to test whether the combined regimen of fludarabine, melphalan and CAMPATH-1H can induce damage to germ cell (GC) and Leydig cell (LC) compartments. Testicular function was assessed immediately prior to transplantation and at four time points post-transplant to compare hormonal levels before and after the procedure. Two other groups treated with BEAM- and TBI-related regimes were also included in the study group for comparative purposes. GC function was assessed by measuring basal serum follicle stimulating hormone (FSH). LC function was assessed by measuring basal luteinising hormone (LH) and testosterone (T) levels. LC reserve was assessed by measuring the T/LH ratio. As a group, patients who received a non myeloablative transplant sustained severe damage to the GC compartment, as evident from a substantial elevation in the FSH level post-transplant (12 IU/l vs 18.4 IU/l, P<0.001). Similar to the GC injury, patients as a group sustained significant damage to the LC compartment following the transplant (5.4 IU/l vs 9.6 IU/l, P<0.001). In general, patients had reduced LC reserve post-BMT, as evident from a diminished T/LH ratio (2.6 pretransplant vs 1.6 post-transplant P=0.05). Patients who received a nonmyeloablative transplant had a similar effect on the GC and LC compartments compared to those who had a BEAM autograft. On the other hand, patients who received a TBI-based transplant sustained more damage to their GC and LC compartments compared to those who received a nonmyeloblative transplant; however, this was not statistically significant (P=0.09). Our data suggest that this type of regimen is potentially gonadotoxic and consideration should be given to fertility counselling and testosterone replacement therapy post-transplant.

Adult↗
PubMed2002

Management of erectile dysfunction by combination therapy with testosterone and sildenafil in recipients of high-dose therapy for haematological malignancies.

Erectile dysfunction (ED) is a well recognised complication of bone marrow transplantation, which affects quality of life in adult patients. Although the major contributory factors include hypogonadism and psychogenic factors, the best treatment still remains to be established due to the complex aetiopathology of the condition. Here, we report our preliminary results in eight patients treated with testosterone replacement therapy and sildenafil. We studied eight male recipients of BMT aged 22-58 years, presenting with clinical features of hypogonadism, ED, diminished libido and ejaculatory disorders. ED was assessed clinically and by colour flow Doppler studies of the cavernosal vessels. Testicular function was assessed by testicular volume, FSH, LH and testosterone (T) measurements. Erectile performance, libido and ejaculatory function were determined by a structured interview. Patients had severe primary hypogonadism as evidenced by low mean testicular volume, elevated gonadotrophins and low normal mean testosterone levels compared with controls. All had Leydig cell insufficiency (LCI) with or without frank serum testosterone insufficiency. All except one had cavernosal arterial insufficiency. All patients received intramuscular injections of testosterone cypionate (250 mg 4 weekly) for 6 months and 50-100 mg of sildenafil orally, one to two times per week. All patients responded favourably as substantiated from the NIH consensus criteria. Our preliminary results suggest that this combined therapy is a safe and effective therapeutic approach in recipients of high-dose therapy presenting with ED after transplant.

Administration, Oral↗
PubMed2002

Treatment of gonadal damage in recipients of allogeneic or autologous transplantation for haematological malignancies.

Management of iatrogenic gonadal reproductive failure and sexual morbidity assumes a priority, especially in young recipients of high-dose chemotherapy and stem cell transplantation (SCT). Hormone replacement treatment (HRT) is beneficial for correction of sexual symptoms and osteoporosis in both sexes, especially in females. Sperm banking is the standard technique for preservation of fertility in adult and sexually mature adolescent males. Testicular tissue cryopreservation has a place in well-selected azoospermic adults and in mentally and sexually competent adolescents. In vitro fertilisation using superovulation with embryo-cryopreservation (for future embryo transfer) is the most tried method in female SCT recipients with good results. In mentally and sexually competent adolescents and adults without a partner, ovarian cortical tissue cryopreservation has a place for subsequent re-implantation to orthotopic or heterotopic sites. Gonadotrophin releasing hormone (GnRH) co-treatment during chemotherapy, is a promising method for the future. Although generally reassuring, continued monitoring of the offspring of SCT survivors and follow-up of all recipients of SCT is important for return of spontaneous or induced fertility.

Female↗
PubMed2002

Ontogeny of human fetal testicular apoptosis during first, second, and third trimesters of pregnancy.

During spermatogenesis in human adults, testicular germ cells proliferate, differentiate, and die by apoptosis. However, little is known about the temporal or spatial nature of this programmed cell death. Such information may be useful for understanding prenatal developmental biology as well as spermatogenesis during adulthood, particularly in the context of germ cell disorders. We undertook this study to determine 1) whether apoptosis occurred in a cell-specific fashion in the germ cell population and the supporting somatic cells; and 2) whether apoptosis varied with gestational age. We examined human fetal testicular tissues obtained from 17 karyotypically and structurally normal fetuses of mothers who underwent spontaneous or induced abortions. Three gestational ages were defined as follows: group A, 12-13 wk gestation (n = 5); group B, 20-22 wk gestation (n = 7); and group C, 37-40 wk gestation (n = 5). Morphology in conjunction with in situ end labeling was used to identify and quantify apoptotic nuclei in fetal gonadal tissues. The results of this study suggest that gonadal apoptosis occurred in germ cells, Sertoli cells, and Leydig cells at all gestational ages. Apoptotic death was highest in the Leydig cells, followed by germ cells and Sertoli cells. There was a significant positive correlation between the apoptosis of germ cells and Sertoli cells (P < 0.01) and a negative correlation between healthy germ cells and Sertoli cells (P < 0.001). There was also a negative correlation between the intratubular cell number and the gestational age. Specifically, the proportion of Sertoli cells decreased with gestational age, although there was no significant change in the germ cell in relation to gestational age. No such relationship was found in the Leydig cell population, all of which reside outside the seminiferous tubules. These results are the first to suggest that fetal testicular apoptosis begins in the first trimester, occurs in the three major cell types, and continues throughout pregnancy. Our data also suggest that in the fetal gonad, germ and Sertoli cell proliferation and death may be controlled by a genetic program distinct from that of the Leydig cells. This information is relevant to the understanding of abnormal spermatogenesis associated with infertility and to germ cell tumors in adult life.

Apoptosis↗
PubMed2001

Pregnancy outcomes after peripheral blood or bone marrow transplantation: a retrospective survey.

BACKGROUND: Some patients treated by transplantation of haemopoietic stem cells (peripheral blood or bone marrow) become permanently infertile, but others retain or recover fertility. We assessed the outcome of conception in women, and partners of men previously treated by autologous or allogeneic stem cell transplantation (SCT). METHODS: We sent questionnaires to 229 centres of the European Group for Blood and Marrow Transplantation. We sought details about the original disease, transplant procedure, and outcome of conception for both male and female patients. FINDINGS: 199 centres gave information relating to 19412 allogeneic and 17950 autologous transplant patients. 232 (0.6%) patients conceived after SCT. Crude annual birth rate for 4-month survivors of SCT was lower than the national average for England and Wales at 1.7 per 1000 patients. 312 conceptions were reported in 113 patients (74 allograft) and partners of 119 patients (93 allograft). Most pregnancies were uncomplicated and resulted in 271 livebirths. 28 (42%) of 67 allograft recipients had caesarean section compared with 16% in the normal population (difference =26% [95% CI 15-38]), 12 (20%) of 59 had preterm delivery compared with a normal rate of 6% (14% [4-24]), and 12 (23%) of 52 had low birthweight singleton offspring compared with a normal rate of 6% (17% [6-29]). INTERPRETATION: Pregnancy after SCT is likely to have a successful outcome. Pregnancies in allograft patients who have received total body irradiation should be treated as high risk for maternal and fetal complications.

Adolescent↗
PubMed2001

Patterns of Leydig cell insufficiency in adult males following bone marrow transplantation for haematological malignancies.

Gonadal and sexual function are key to quality of life following bone marrow transplantation (BMT), but no large studies have been published on Leydig cell (LC) function in adults. LC insufficiency (LCI) can cause premature andropause with its consequences including sexual morbidity from diminished libido and erectile dysfunction (ED). In addition, LCI can result in generalised fatigue and even osteopenia. We reviewed gonadal function pre-transplant (immediately prior to BMT) and at 3-18 months post BMT in 117 patients who underwent BMT for a variety of haematological malignancies. The patients presented with variable degrees of symptoms of LCI, such as fatigue, diminished sex drive and libido or ED. The results suggest that the patients sustained severe gonadal damage to both their germ cells (GC) as well as the LC compartment (P < 0.001). We characterised two distinct functional subsets of LC insufficiency: Type I: compensated type with high LH and normal T levels and low T/LH ratio: (n = 102); and type II: uncompensated type (premature andropause) with high LH and low testosterone levels with low T/LH ratio (n = 15). Although type II patients had more severe LC damage than type I, patients in both groups were symptomatic. We recommend that symptomatic patients in both groups may benefit from a therapeutic trial with testosterone replacement treatment (TRT) for 3-6 months.

Adolescent↗
PubMed2001

Hypogonadotrophism fails to prevent severe testicular damage induced by total body irradiation in a patient with beta-thalassaemia major and acute lymphoblastic leukaemia.

Radiation and chemotherapeutic drugs for cancer produce prolonged and often irreversible gonadal damage. To determine whether total body irradiation (TBI)-induced gonadal damage can be prevented by suppression of pituitary gonadotrophin levels, we studied a patient with transfusion dependent homozygous beta-thalassaemia and acute lymphoblastic leukaemia (ALL) who underwent one-antigen mismatched related bone marrow transplantation (BMT). Our data showed that despite having hypogonadotrophic hypogonadism (HH) prior to BMT, the patient developed primary testicular failure following the procedure, indicating that hypogonadotrophism failed to offer protection against TBI-induced testicular damage in this patient. Although this is an interesting case report, no firm conclusions can be drawn from a single patient.

Adult↗
PubMed2001

Gynaecomastia with hypergonadotrophic hypogonadism and Leydig cell insufficiency in recipients of high-dose chemotherapy or chemo-radiotherapy.

Late side-effects of stem cell transplantation include hypogonadism with infertility and sexual dysfunction, but gynaecomastia is less well recognised. We report five cases of gynaecomastia with features of hypergonadotrophic hypogonadism (primary testicular failure), who received either a TBI/cyclophosphamide conditioned allograft (n = 3) or a BEAM autograft (n = 2). Patients receiving an allograft had gynaecomastia, Leydig cell insufficiency (LCI) diminished libido and erectile dysfunction. Surgery was required in one case, while in two cases the gynaecomastia resolved spontaneously after 6 months. Two patients also had gynaecomastia and sexual dysfunction, severe hypogonadism, very low testosterone levels and marked hyperprolactinaemia following autoBMT. Both responded well to testosterone replacement therapy (TRT). As a group, all patients had primary testicular failure and all except one, had LCI (compensated or frank). However, there was no correlation between the severity of gynaecomastia and the degree of endocrine dysfunction. This preliminary study is the first to suggest that gynaecomastia, due to primary hypogonadism and LCI, may be a significant complication of myeloablative conditioning therapy. Therefore gynaecomastia in BMT recipients must always be treated as a pathological entity as it may be the external manifestation of a complex endocrine pathology. It is a potentially treatable condition. Although spontaneously reversible, some patients may require TRT or even surgery. We recommend comprehensive endocrine testing in conjunction with a reproductive endocrinologist and prompt intervention to alleviate embarrassment and anxiety in afflicted BMT recipients.

Adult↗
PubMed2001

Imaging human mesolimbic dopamine transmission with positron emission tomography: I. Accuracy and precision of D(2) receptor parameter measurements in ventral striatum.

Dopamine transmission in the ventral striatum (VST), a structure which includes the nucleus accumbens, ventral caudate, and ventral putamen, plays a critical role in the pathophysiology of psychotic states and in the reinforcing effects of virtually all drugs of abuse. The aim of this study was to assess the accuracy and precision of measurements of D(2) receptor availability in the VST obtained with positron emission tomography on the high-resolution ECAT EXACT HR+ scanner (Siemens Medical Systems, Knoxville, TN, U.S.A.). A method was developed for identification of the boundaries of the VST on coregistered high-resolution magnetic resonance imaging scans. Specific-to-nonspecific partition coefficient (V(3)") and binding potential (BP) of [(11)C]raclopride were measured twice in 10 subjects, using the bolus plus constant infusion method. [(11)C]Raclopride V(3)" in the VST (1.86 +/- 0.29) was significantly lower than in the dorsal caudate (DCA, 2.33 +/- 0.28) and dorsal putamen (DPU, 2.99 +/- 0.26), an observation consistent with postmortem studies. The reproducibility of V(3)" and BP were appropriate and similar in VST (V(3)" test-retest variability of 8.2% +/- 6.2%, intraclass correlation coefficient = 0.83), DCA (7.7% +/- 5.1%, 0.77), DPU (6.0% +/- 4.1%, 0.71), and striatum as a whole (6.3% +/- 4.1%, 0.78). Partial volume effects analysis revealed that activities in the VST were significantly contaminated by counts spilling over from the adjacent DCA and DPU: 70% +/- 5% of the specific binding measured in the VST originated from D(2) receptors located in the VST, whereas 12% +/- 3% and 18% +/- 3% were contributed by D(2) receptors in the DCA and DPU, respectively. Thus, accuracy of D(2) receptor measurement is improved by correction for partial voluming effects. The demonstration of an appropriate accuracy and precision of D(2) receptor measurement with [(11)C]raclopride in the VST is the first critical step toward the use of this ligand in the study of synaptic dopamine transmission at D(2) receptors in the VST using endogenous competition techniques.

Adult↗
PubMed2001

Mutation of the ptsG gene results in increased production of succinate in fermentation of glucose by Escherichia coli.

Escherichia coli NZN111 is blocked in the ability to grow fermentatively on glucose but gave rise spontaneously to a mutant that had this ability. The mutant carries out a balanced fermentation of glucose to give approximately 1 mol of succinate, 0. 5 mol of acetate, and 0.5 mol of ethanol per mol of glucose. The causative mutation was mapped to the ptsG gene, which encodes the membrane-bound, glucose-specific permease of the phosphotransferase system, protein EIICB(glc). Replacement of the chromosomal ptsG gene with an insertionally inactivated form also restored growth on glucose and resulted in the same distribution of fermentation products. The physiological characteristics of the spontaneous and null mutants were consistent with loss of function of the ptsG gene product; the mutants possessed greatly reduced glucose phosphotransferase activity and lacked normal glucose repression. Introduction of the null mutant into strains not blocked in the ability to ferment glucose also increased succinate production in those strains. This phenomenon was widespread, occurring in different lineages of E. coli, including E. coli B.

Alleles↗
PubMed2001

Human immunodeficiency virus type 1 env sequences from Calcutta in eastern India: identification of features that distinguish subtype C sequences in India from other subtype C sequences.

India is experiencing a rapid spread of human immunodeficiency virus type 1 (HIV-1), primarily through heterosexual transmission of subtype C viruses. To delineate the molecular features of HIV-1 circulating in India, we sequenced the V3-V4 region of viral env from 21 individuals attending an HIV clinic in Calcutta, the most populous city in the eastern part of the country, and analyzed these and the other Indian sequences in the HIV database. Twenty individuals were infected with viruses having a subtype C env, and one had viruses with a subtype A env. Analyses of 192 subtype C sequences that included one sequence for each subject from this study and from the HIV database revealed that almost all sequences from India, along with a small number from other countries, form a phylogenetically distinct lineage within subtype C, which we designate C(IN). Overall, C(IN) lineage sequences were more closely related to each other (level of diversity, 10.2%) than to subtype C sequences from Botswana, Burundi, South Africa, Tanzania, and Zimbabwe (range, 15.3 to 20.7%). Of the three positions identified as signature amino acid substitution sites for C(IN) sequences (K340E, K350A, and G429E), 56% of the C(IN) sequences contained all three amino acids while 87% of the sequences contained at least two of these substitutions. Among the non-C(IN) sequences, all three amino acids were present in 2%, while 22% contained two or more of these amino acids. These results suggest that much of the current Indian epidemic is descended from a single introduction into the country. Identification of conserved signature amino acid positions could assist epidemiologic tracking and has implications for the development of a vaccine against subtype C HIV-1 in India.

Adult↗
PubMed2001

Evaluation of gonadotrophin insufficiency in thalassemic boys with pubertal failure: spontaneous versus provocative test.

The objective of this study was to determine whether iron toxicity in blood transfusion dependent beta-thalassemic patients with pubertal failure was associated with gonadotrophin (GTH) insufficiency as assessed by spontaneous and dynamic tests. Gonadotrophin-releasing-hormone (GnRH)-GTH secretory dynamics were studied by serial ultradian GTH profiles and a 100 microg i.v. GnRH bolus test (GBT) in 28 male beta-thalassemia major patients with failed puberty (FP group). Five healthy, non thalassemic prepubertal males were studied for comparative purposes. According to the pulse profile, patients in the FP group were subdivided into apulsatile (no FSH and LH pulses, n = 16; AFP group) and pulsatile (defective pulse profile, n = 12; PFP group) subsets. The FP group had lower basal FSH (p < 0.01), LH (p < 0.01) and GnRH stimulated FSH (p < 0.001) and LH levels (p < 0.001) than the controls. However, basal and GnRH-stimulated FSH (p < 0.01 for basal and p < 0.001 for peak) and LH (p < 0.01 for both basal and peak) levels were lower in the AFP than the PFP group. Serum ferritin levels in GnRH-non-responders were higher than those in the responders (9,052.63 +/- 579.14 mg/l vs 5,933.33 +/- 1,819.65 mg/l; p < 0.05). Similarly, symptomatic organ damage was higher in the AFP than the PFP patients (81% vs 42%; p < 0.001). In conclusion, this study suggests that iron overloaded thalassemic patients with failed puberty had abnormal GnRH-GTH secretory dynamics. The severity of the defect was heterogeneous, ranging from very severe (apulsatile) to less severe (pulsatile) subsets. Comparison between spontaneous and dynamic test levels showed that there was concordance between the degree of pulse defect and magnitude of LH response to GBT. However, ultradian GTH profile was a more reliable method for identifying the degree of GTH insufficiency than GBT. Our data also showed that iron toxicity was the major cause of GnRH-GTH deficiency in thalassemic patients. Such information may be useful for better understanding of the pathophysiology of hypogonadotrophic hypogonadism (HH), thereby promoting therapeutic options for induction of puberty and spermatogenesis.

Adolescent↗
PubMed2001

Reversal of fludarabine induced testicular damage in a patient with chronic lymphocytic leukaemia (CLL), by suppression of pituitary-testicular axis using gonadotrophin releasing hormone (GnRH).

We describe a case of a 47 year old man with CLL who was treated with 7 courses of fludarabine with simultaneous suppression of his pituitary-testicular axis (P-T) with Gonadotrophin releasing hormone (GnRH) and replacement treatment with testosterone. Despite initial gonadal damage as evident by endocrine and sperm studies, testicular recovery was observed 11 months post treatment. Although spontaneous recovery cannot be ruled out, continuous treatment with GnRH and testosterone may play a crucial role protecting the gonads from the cytotoxic effects of the chemotherapeutic agents.

Antineoplastic Agents↗
PubMed2001

Prevalence of human papillomavirus infection among prostitutes in Calcutta.

We investigated the presence of human papilloma virus (HPV) 16/18 and herpes simplex virus-1,-2 (HSV-1,-2) infections in buccal mucosal cells of prostitutes of Calcutta, India, by in situ DNA hybridization and immunocytochemical technique. In some of them, we also examined the prevalence of viral infections in uterine cervical cells. The women were also tested for venereal disease research laboratory antigen (VDRL) positivity. Oral infections with HSV-1, -2 and HPV 16/18 were detected in 24.6%, 11.6%, and 29%, respectively. Similar cervical infections were found in 0%, 44%, and 62.9% of the cases studied. HPV coinfection was significantly higher (p < 0.01) in both the oral and cervical cells that had HSV infection. The cervical HPV infections were not markedly higher among the VDRL-positive prostitutes (p > 0.05). The HPV or HSV infection rates showed no remarkable variation between the two age groups of the prostitutes studied (p > 0.05). Cytological abnormalities were more pronounced in the cervix of women having concurrent infection with HPV and HSV-2 rather than in the presence of infection with either of the two. This preliminary investigation, the first of its kind in India, requires a larger study to understand the significance of the association of different sexually transmitted agents including HPV (apart from HIV) as risk factors for pathologic lesions.

Adult↗
PubMed2001

Ethmocephaly.

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Abnormalities, Multiple↗
PubMed2000

One antigen mismatched related donor bone marrow transplant in a patient with acute lymphoblastic leukaemia and beta-thalassaemia major: potential cure of both marrow disorders.

We report a case of a 34-year-old man with T-ALL and beta-thalassaemia major who underwent a one antigen mismatched related donor bone marrow transplant. Five months post transplant chimeric studies revealed full donor haemopoiesis and the patient remains leukaemia and thalassaemia free at 12 months post transplant. Cumulative risk factors contributing to the increased transplant-related mortality in patients with two different marrow disorders are discussed.

Adult↗
PubMed2000

Cavernosal arterial insufficiency is a major component of erectile dysfunction in some recipients of high-dose chemotherapy/chemo-radiotherapy for haematological malignancies.

We studied 24 male patients aged 26-62 years (median 41) prospectively presenting over a 5 year period with clinical features of hypogonadism and erectile dysfunction (ED), who had been treated with autologous or allogeneic bone marrow/stem cell transplant for a variety of haematological malignancies and had received either high-dose chemotherapy or high-dose chemotherapy combined with total body irradiation (TBI). Ten healthy adult controls (aged 35-50 years) were also studied. Erectile dysfunction (ED) was assessed clinically and by colour flow Doppler studies of the cavernosal vessels. Testicular function was assessed by testicular volume including orchidometry, FSH, LH and testosterone measurements. Libido and ejaculatory function were also recorded. Patients had severe hypogonadism as evidenced by low mean testicular volume (7.0 +/- 2.4 ml vs 20 +/- 2.0 ml; P < 0.001), elevated gonadotrophins (FSH = 18.54 +/- 7.61 vs 5 IU/l (P < 0.001); LH = 8.02 +/- 2.89 vs 3. 9 IU/l (P < 0.001)) and low normal mean testosterone levels (16.4 nmol/l +/- 9.1 vs 22.4 nmol/l (P < 0.5)). Cavernosal arterial insufficiency was found in 11/14 of TBI-treated and in 3/10 HDC-treated patients, indicative of vasculogenic damage to corpora cavernosal vessels. Patients were given a therapeutic trial with testosterone replacement therapy (TRT). Those who had diminished libido had a marked improvement in their symptoms but the effect of TRT on ED was equivocal. In conclusion, this is the first report to show vasculogenic insufficiency in patients with haematological malignancies treated by BMT. Although hypogonadism can account for diminished libido, arteriogenic insufficiency is likely to be an important factor accounting for ED in these patients, especially those treated by TBI. We recommend a comprehensive assessment including endocrine profile and colour flow Doppler study in formulating the best management plan in recipients of high-dose therapy presenting after transplant with ED.

Adult↗